Computational and Experimental Approaches to Investigate Lipid Nanoparticles as Drug and Gene Delivery Systems

Chun       Chan; Shi       Du; Yizhou       Dong; Xiaolin       Cheng
doi:10.2174/1568026620666201126162945
Abstract

Lipid nanoparticles (LNPs) have been widely applied in drug and gene delivery. More than twenty years ago, Doxil^TM was the first LNPs-based drug approved by the US Food and Drug Administration (FDA). Since then, with decades of research and development, more and more LNP-based therapeutics have been used to treat diverse diseases, which often offer the benefits of reduced toxicity and/or enhanced efficacy compared to the active ingredients alone. Here, we provide a review of recent advances in the development of efficient and robust LNPs for drug/gene delivery. We emphasize the importance of rationally combining experimental and computational approaches, especially those providing multiscale structural and functional information of LNPs, to the design of novel and powerful LNP-based delivery systems.
Keywords: Lipid nanoparticle, Drug delivery, Gene delivery, Multiscale molecular simulation, Molecular dynamics, Machine learning.
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[1] 
Pattni, B.S.; Chupin, V.V.; Torchilin, V.P. New developments in liposomal drug delivery. Chem. Rev.,  2015, 115(19), 10938-10966.
[http://dx.doi.org/10.1021/acs.chemrev.5b00046] [PMID: 26010257] 
[2] 
Allen, T.M.; Cullis, P.R. Liposomal drug delivery systems: from concept to clinical applications. Adv. Drug Deliv. Rev.,  2013, 65(1), 36-48.
[http://dx.doi.org/10.1016/j.addr.2012.09.037] [PMID: 23036225] 
[3] 
Akinc, A.; Maier, M.A.; Manoharan, M.; Fitzgerald, K.; Jayaraman, M.; Barros, S.; Ansell, S.; Du, X.; Hope, M.J.; Madden, T.D.; Mui, B.L.; Semple, S.C.; Tam, Y.K.; Ciufolini, M.; Witzigmann, D.; Kulkarni, J.A.; van der Meel, R.; Cullis, P.R. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol.,  2019, 14(12), 1084-1087.
[http://dx.doi.org/10.1038/s41565-019-0591-y] [PMID: 31802031] 
[4] 
Akinc, A.; Zumbuehl, A.; Goldberg, M.; Leshchiner, E.S.; Busini, V.; Hossain, N.; Bacallado, S.A.; Nguyen, D.N.; Fuller, J.; Alvarez, R.; Borodovsky, A.; Borland, T.; Constien, R.; de Fougerolles, A.; Dorkin, J.R.; Narayanannair Jayaprakash, K.; Jayaraman, M.; John, M.; Koteliansky, V.; Manoharan, M.; Nechev, L.; Qin, J.; Racie, T.; Raitcheva, D.; Rajeev, K.G.; Sah, D.W.Y.; Soutschek, J.; Toudjarska, I.; Vornlocher, H-P.; Zimmermann, T.S.; Langer, R.; Anderson, D.G. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat. Biotechnol.,  2008, 26(5), 561-569.
[http://dx.doi.org/10.1038/nbt1402] [PMID: 18438401] 
[5] 
Bangham, A.D.; Horne, R.W. Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. J. Mol. Biol.,  1964, 8, 660-668.
[http://dx.doi.org/10.1016/S0022-2836(64)80115-7] [PMID: 14187392] 
[6] 
Bangham, A.D.; Standish, M.M.; Watkins, J.C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol.,  1965, 13(1), 238-252.
[http://dx.doi.org/10.1016/S0022-2836(65)80093-6] [PMID: 5859039] 
[7] 
Sessa, G.; Weissmann, G. Phospholipid spherules (liposomes) as a model for biological membranes. J. Lipid Res.,  1968, 9(3), 310-318.
[PMID: 5646182] 
[8] 
Butu, A.; Rodino, S.; Golea, D.; Butu, M.; Butnariu, M.; Negoescu, C.; Dinu-Pirvu, C-E. Liposomal nanodelivery system for proteasome inhibitor anticancer drug bortezomib. Farmacia,  2015, 63, 224-229.
[9] 
Xu, X.; Saw, P.E.; Tao, W.; Li, Y.; Ji, X.; Bhasin, S.; Liu, Y.; Ayyash, D.; Rasmussen, J.; Huo, M.; Shi, J.; Farokhzad, O.C. ROS-responsive polyprodrug nanoparticles for triggered drug delivery and effective cancer therapy. Adv. Mater.,  2017, 29(33)1700141
[http://dx.doi.org/10.1002/adma.201700141] [PMID: 28681981] 
[10] 
Lin, Y-X.; Wang, Y.; An, H-W.; Qi, B.; Wang, J.; Wang, L.; Shi, J.; Mei, L.; Wang, H. Peptide-based autophagic gene and cisplatin co-delivery systems enable improved chemotherapy resistance. Nano Lett.,  2019, 19(5), 2968-2978.
[http://dx.doi.org/10.1021/acs.nanolett.9b00083] [PMID: 30924343] 
[11] 
Shi, J.; Xiao, Z.; Votruba, A.R.; Vilos, C.; Farokhzad, O.C. Differentially charged hollow core/shell lipid-polymer-lipid hybrid nanoparticles for small interfering RNA delivery. Angew. Chem. Int. Ed. Engl.,  2011, 50(31), 7027-7031.
[http://dx.doi.org/10.1002/anie.201101554] [PMID: 21698724] 
[12] 
Xue, Y.; Feng, J.; Liu, Y.; Che, J.; Bai, G.; Dong, X.; Wu, F.; Jin, T. A synthetic carrier of nucleic acids structured as a neutral phospholipid envelope tightly assembled on polyplex surface. Adv. Healthc. Mater.,  2020, 9(6)e1901705
[http://dx.doi.org/10.1002/adhm.201901705] [PMID: 31977157] 
[13] 
Russick, J.; Delignat, S.; Milanov, P.; Christophe, O.; Boros, G.; Denis, C.V.; Lenting, P.J.; Kaveri, S.V.; Lacroix-Demazes, S. Correction of bleeding in experimental severe hemophilia a by systemic delivery of factor viii-encoding mrna. haematologica, 2020, 105, 11129-1137.
[14] 
James, N.D.; Coker, R.J.; Tomlinson, D.; Harris, J.R.W.; Gompels, M.; Pinching, A.J.; Stewart, J.S.W. Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi’s sarcoma in AIDS. Clin. Oncol. (R. Coll. Radiol.),  1994, 6(5), 294-296.
[http://dx.doi.org/10.1016/S0936-6555(05)80269-9] [PMID: 7530036] 
[15] 
Barenholz, Y. Doxil®--the first FDA-approved nano-drug: lessons learned. J. Control. Release,  2012, 160(2), 117-134.
[http://dx.doi.org/10.1016/j.jconrel.2012.03.020] [PMID: 22484195] 
[16] 
Beltrán-Gracia, E.; López-Camacho, A.; Higuera-Ciapara, I.; Velázquez-Fernández, J.B.; Vallejo-Cardona, A.A. Nanomedicine review: clinical developments in liposomal applications. Cancer Nano,  2019, 10, 11.
[http://dx.doi.org/10.1186/s12645-019-0055-y] 
[17] 
Maurer, N.; Fenske, D.B.; Cullis, P.R. Developments in liposomal drug delivery systems. Expert Opin. Biol. Ther.,  2001, 1(6), 923-947.
[http://dx.doi.org/10.1517/14712598.1.6.923] [PMID: 11728226] 
[18] 
Park, H-J.; Yang, F.; Cho, S-W. Nonviral delivery of genetic medicine for therapeutic angiogenesis. Adv. Drug Deliv. Rev.,  2012, 64(1), 40-52.
[http://dx.doi.org/10.1016/j.addr.2011.09.005] [PMID: 21971337] 
[19] 
Cullis, P.R.; Hope, M.J. Lipid nanoparticle systems for enabling gene therapies. Mol. Ther.,  2017, 25(7), 1467-1475.
[http://dx.doi.org/10.1016/j.ymthe.2017.03.013] [PMID: 28412170] 
[20] 
Mukalel, A.J.; Riley, R.S.; Zhang, R.; Mitchell, M.J. Nanoparticles for nucleic acid delivery: Applications in cancer immunotherapy. Cancer Lett.,  2019, 458, 102-112.
[http://dx.doi.org/10.1016/j.canlet.2019.04.040] [PMID: 31100411] 
[21] 
Veiga, N.; Diesendruck, Y.; Peer, D. Targeted lipid nanoparticles for RNA therapeutics and immunomodulation in leukocytes. Adv. Drug Deliv. Rev.,,  2020, S0169-409X(20), 30022-3.
[PMID: 32298783] 
[22] 
Hoffman, R.M.; Margolis, L.B.; Bergelson, L.D. Binding and entrapment of high molecular weight DNA by lecithin liposomes. FEBS Lett.,  1978, 93(2), 365-368.
[http://dx.doi.org/10.1016/0014-5793(78)81141-7] [PMID: 568565] 
[23] 
Mannino, R.J.; Allebach, E.S.; Strohl, W.A. Encapsulation of high molecular weight DNA in large unilamellar phospholipid vesicles. Dependence on the size of the DNA. FEBS Lett.,  1979, 101(2), 229-232.
[http://dx.doi.org/10.1016/0014-5793(79)81014-5] [PMID: 446747] 
[24] 
Dimitriadis, G.J. Entrapment of ribonucleic acids in liposomes. FEBS Lett.,  1978, 86(2), 289-293.
[http://dx.doi.org/10.1016/0014-5793(78)80582-1] [PMID: 624413] 
[25] 
Fraley, R.; Straubinger, R.M.; Rule, G.; Springer, E.L.; Papahadjopoulos, D. Liposome-mediated delivery of deoxyribonucleic acid to cells: enhanced efficiency of delivery related to lipid composition and incubation conditions. Biochemistry,  1981, 20(24), 6978-6987.
[http://dx.doi.org/10.1021/bi00527a031] [PMID: 6274382] 
[26] 
Fraley, R.; Subramani, S.; Berg, P.; Papahadjopoulos, D. Introduction of liposome-encapsulated SV40 DNA into cells. J. Biol. Chem.,  1980, 255(21), 10431-10435.
[PMID: 6253474] 
[27] 
Felgner, P.L.; Gadek, T.R.; Holm, M.; Roman, R.; Chan, H.W.; Wenz, M.; Northrop, J.P.; Ringold, G.M.; Danielsen, M. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc. Natl. Acad. Sci. USA,  1987, 84(21), 7413-7417.
[http://dx.doi.org/10.1073/pnas.84.21.7413] [PMID: 2823261] 
[28] 
Vangasseri, D.P.; Cui, Z.; Chen, W.; Hokey, D.A.; Falo, L.D., Jr; Huang, L. Immunostimulation of dendritic cells by cationic liposomes. Mol. Membr. Biol.,  2006, 23(5), 385-395.
[http://dx.doi.org/10.1080/09687860600790537] [PMID: 17060156] 
[29] 
Filion, M.C.; Phillips, N.C. Toxicity and immunomodulatory activity of liposomal vectors formulated with cationic lipids toward immune effector cells. Biochim. Biophys. Acta,  1997, 1329(2), 345-356.
[http://dx.doi.org/10.1016/S0005-2736(97)00126-0] [PMID: 9371426] 
[30] 
Semple, S.C.; Klimuk, S.K.; Harasym, T.O.; Dos Santos, N.; Ansell, S.M.; Wong, K.F.; Maurer, N.; Stark, H.; Cullis, P.R.; Hope, M.J.; Scherrer, P. Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures. Biochim. Biophys. Acta,  2001, 1510(1-2), 152-166.
[http://dx.doi.org/10.1016/S0005-2736(00)00343-6] [PMID: 11342155] 
[31] 
Adams, D.; Gonzalez-Duarte, A.; O’Riordan, W.D.; Yang, C-C.; Ueda, M.; Kristen, A.V.; Tournev, I.; Schmidt, H.H.; Coelho, T.; Berk, J.L.; Lin, K-P.; Vita, G.; Attarian, S.; Planté-Bordeneuve, V.; Mezei, M.M.; Campistol, J.M.; Buades, J.; Brannagan, T.H., III; Kim, B.J.; Oh, J.; Parman, Y.; Sekijima, Y.; Hawkins, P.N.; Solomon, S.D.; Polydefkis, M.; Dyck, P.J.; Gandhi, P.J.; Goyal, S.; Chen, J.; Strahs, A.L.; Nochur, S.V.; Sweetser, M.T.; Garg, P.P.; Vaishnaw, A.K.; Gollob, J.A.; Suhr, O.B. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N. Engl. J. Med.,  2018, 379(1), 11-21.
[http://dx.doi.org/10.1056/NEJMoa1716153] [PMID: 29972753] 
[32] 
Ickenstein, L.M.; Garidel, P. Lipid-based nanoparticle formulations for small molecules and RNA drugs. Expert Opin. Drug Deliv.,  2019, 16(11), 1205-1226.
[http://dx.doi.org/10.1080/17425247.2019.1669558] [PMID: 31530041] 
[33] 
Anselmo, A.C.; Mitragotri, S. Nanoparticles in the clinic: An update. Bioeng. Transl. Med.,  2019, 4(3)e10143
[http://dx.doi.org/10.1002/btm2.10143] [PMID: 31572799] 
[34] 
Ahmed, K.S.; Hussein, S.A.; Ali, A.H.; Korma, S.A.; Lipeng, Q.; Jinghua, C. Liposome: composition, characterisation, preparation, and recent innovation in clinical applications. J. Drug Target.,  2019, 27(7), 742-761.
[http://dx.doi.org/10.1080/1061186X.2018.1527337] [PMID: 30239255] 
[35] 
Fenske, D.B.; Cullis, P.R. Liposomal nanomedicines. Expert Opin. Drug Deliv.,  2008, 5(1), 25-44.
[http://dx.doi.org/10.1517/17425247.5.1.25] [PMID: 18095927] 
[36] 
Fenske, D.B.; Chonn, A.; Cullis, P.R. Liposomal nanomedicines: an emerging field. Toxicol. Pathol.,  2008, 36(1), 21-29.
[http://dx.doi.org/10.1177/0192623307310960] [PMID: 18337218] 
[37] 
Puri, A.; Loomis, K.; Smith, B.; Lee, J-H.; Yavlovich, A.; Heldman, E.; Blumenthal, R. Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic. Crit. Rev. Ther. Drug Carrier Syst.,  2009, 26(6), 523-580.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v26.i6.10] [PMID: 20402623] 
[38] 
Hattori, Y.; Suzuki, S.; Kawakami, S.; Yamashita, F.; Hashida, M. The role of dioleoylphosphatidylethanolamine (DOPE) in targeted gene delivery with mannosylated cationic liposomes via intravenous route. J. Control. Release,  2005, 108(2-3), 484-495.
[http://dx.doi.org/10.1016/j.jconrel.2005.08.012] [PMID: 16181701] 
[39] 
Edidin, M. Lipids on the frontier: a century of cell-membrane bilayers. Nat. Rev. Mol. Cell Biol.,  2003, 4(5), 414-418.
[http://dx.doi.org/10.1038/nrm1102] [PMID: 12728275] 
[40] 
Shim, G.; Kim, M-G.; Park, J.Y.; Oh, Y-K. Application of cationic liposomes for delivery of nucleic acids. Asian J. Pharma. Sci.,  2013, 8, 72-80.
[http://dx.doi.org/10.1016/j.ajps.2013.07.009] 
[41] 
Kohli, A.G.; Walsh, C.L.; Szoka, F.C. Synthesis and characterization of betaine-like diacyl lipids: zwitterionic lipids with the cationic amine at the bilayer interface. Chem. Phys. Lipids,  2012, 165(2), 252-259.
[http://dx.doi.org/10.1016/j.chemphyslip.2012.01.005] [PMID: 22301334] 
[42] 
Perttu, E.K.; Szoka, F.C., Jr Zwitterionic sulfobetaine lipids that form vesicles with salt-dependent thermotropic properties. Chem. Commun. (Camb.),  2011, 47(47), 12613-12615.
[http://dx.doi.org/10.1039/c1cc15804j] [PMID: 22045250] 
[43] 
Luo, C.; Miao, L.; Zhao, Y.; Musetti, S.; Wang, Y.; Shi, K.; Huang, L. A novel cationic lipid with intrinsic antitumor activity to facilitate gene therapy of TRAIL DNA. Biomaterials,  2016, 102, 239-248.
[http://dx.doi.org/10.1016/j.biomaterials.2016.06.030] [PMID: 27344367] 
[44] 
Miao, L.; Li, L.; Huang, Y.; Delcassian, D.; Chahal, J.; Han, J.; Shi, Y.; Sadtler, K.; Gao, W.; Lin, J.; Doloff, J.C.; Langer, R.; Anderson, D.G. Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation. Nat. Biotechnol.,  2019, 37(10), 1174-1185.
[http://dx.doi.org/10.1038/s41587-019-0247-3] [PMID: 31570898] 
[45] 
Walsh, C.L.; Nguyen, J.; Tiffany, M.R.; Szoka, F.C. Synthesis, characterization, and evaluation of ionizable lysine-based lipids for siRNA delivery. Bioconjug. Chem.,  2013, 24(1), 36-43.
[http://dx.doi.org/10.1021/bc300346h] [PMID: 23176544] 
[46] 
Zuhorn, I.S.; Hoekstra, D. On the mechanism of cationic amphiphile-mediated transfection. To fuse or not to fuse: is that the question? J. Membr. Biol.,  2002, 189(3), 167-179.
[http://dx.doi.org/10.1007/s00232-002-1015-7] [PMID: 12395282] 
[47] 
Zhi, D.; Bai, Y.; Yang, J.; Cui, S.; Zhao, Y.; Chen, H.; Zhang, S. A review on cationic lipids with different linkers for gene delivery. Adv. Colloid Interface Sci.,  2018, 253, 117-140.
[http://dx.doi.org/10.1016/j.cis.2017.12.006] [PMID: 29454463] 
[48] 
Ramishetti, S.; Hazan-Halevy, I.; Palakuri, R.; Chatterjee, S.; Naidu Gonna, S.; Dammes, N.; Freilich, I.; Kolik Shmuel, L.; Danino, D.; Peer, D. A Combinatorial library of lipid nanoparticles for rna delivery to leukocytes. Adv. Mater.,  2020, 32(12)e1906128
[http://dx.doi.org/10.1002/adma.201906128] [PMID: 31999380] 
[49] 
Zhi, D.; Zhang, S.; Wang, B.; Zhao, Y.; Yang, B.; Yu, S. Transfection efficiency of cationic lipids with different hydrophobic domains in gene delivery. Bioconjug. Chem.,  2010, 21(4), 563-577.
[http://dx.doi.org/10.1021/bc900393r] [PMID: 20121120] 
[50] 
Zhi, D.; Zhang, S.; Cui, S.; Zhao, Y.; Wang, Y.; Zhao, D. The headgroup evolution of cationic lipids for gene delivery. Bioconjug. Chem.,  2013, 24(4), 487-519.
[http://dx.doi.org/10.1021/bc300381s] [PMID: 23461774] 
[51] 
Hattori, Y.; Kawakami, S.; Suzuki, S.; Yamashita, F.; Hashida, M. Enhancement of immune responses by DNA vaccination through targeted gene delivery using mannosylated cationic liposome formulations following intravenous administration in mice. Biochem. Biophys. Res. Commun.,  2004, 317(4), 992-999.
[http://dx.doi.org/10.1016/j.bbrc.2004.03.141] [PMID: 15094367] 
[52] 
Dow, S.W.; Fradkin, L.G.; Liggitt, D.H.; Willson, A.P.; Heath, T.D.; Potter, T.A. Lipid-DNA complexes induce potent activation of innate immune responses and antitumor activity when administered intravenously. J. Immunol.,  1999, 163(3), 1552-1561.
[PMID: 10415059] 
[53] 
Pippa, N.; Pispas, S.; Demetzos, C. The delineation of the morphology of charged liposomal vectors via a fractal analysis in aqueous and biological media: physicochemical and self-assembly studies. Int. J. Pharm.,  2012, 437(1-2), 264-274.
[http://dx.doi.org/10.1016/j.ijpharm.2012.08.017] [PMID: 22939965] 
[54] 
Heyes, J.; Palmer, L.; Bremner, K.; MacLachlan, I. Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids. J. Control. Release,  2005, 107(2), 276-287.
[http://dx.doi.org/10.1016/j.jconrel.2005.06.014] [PMID: 16054724] 
[55] 
Jayaraman, M.; Ansell, S.M.; Mui, B.L.; Tam, Y.K.; Chen, J.; Du, X.; Butler, D.; Eltepu, L.; Matsuda, S.; Narayanannair, J.K.; Rajeev, K.G.; Hafez, I.M.; Akinc, A.; Maier, M.A.; Tracy, M.A.; Cullis, P.R.; Madden, T.D.; Manoharan, M.; Hope, M.J. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. Angew. Chem. Int. Ed. Engl.,  2012, 51(34), 8529-8533.
[http://dx.doi.org/10.1002/anie.201203263] [PMID: 22782619] 
[56] 
Alabi, C.A.; Love, K.T.; Sahay, G.; Yin, H.; Luly, K.M.; Langer, R.; Anderson, D.G. Multiparametric approach for the evaluation of lipid nanoparticles for siRNA delivery. Proc. Natl. Acad. Sci. USA,  2013, 110(32), 12881-12886.
[http://dx.doi.org/10.1073/pnas.1306529110] [PMID: 23882076] 
[57] 
Wang, M.; Zuris, J.A.; Meng, F.; Rees, H.; Sun, S.; Deng, P.; Han, Y.; Gao, X.; Pouli, D.; Wu, Q.; Georgakoudi, I.; Liu, D.R.; Xu, Q. Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles. Proc. Natl. Acad. Sci. USA,  2016, 113(11), 2868-2873.
[http://dx.doi.org/10.1073/pnas.1520244113] [PMID: 26929348] 
[58] 
Wei, T.; Cheng, Q.; Min, Y-L.; Olson, E.N.; Siegwart, D.J. Systemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing. Nat. Commun.,  2020, 11(1), 3232.
[http://dx.doi.org/10.1038/s41467-020-17029-3] [PMID: 32591530] 
[59] 
Cheng, Q.; Wei, T.; Farbiak, L.; Johnson, L.T.; Dilliard, S.A.; Siegwart, D.J. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing. Nat. Nanotechnol.,  2020, 15(4), 313-320.
[http://dx.doi.org/10.1038/s41565-020-0669-6] [PMID: 32251383] 
[60] 
Cheng, X.; Lee, R.J. The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery. Adv. Drug Deliv. Rev., 2016, 99(Pt A), 129-137.
[http://dx.doi.org/10.1016/j.addr.2016.01.022] [PMID: 26900977] 
[61] 
Sakurai, F.; Nishioka, T.; Yamashita, F.; Takakura, Y.; Hashida, M. Effects of erythrocytes and serum proteins on lung accumulation of lipoplexes containing cholesterol or DOPE as a helper lipid in the single-pass rat lung perfusion system. Eur. J. Pharm. Biopharm.,  2001, 52(2), 165-172.
[http://dx.doi.org/10.1016/S0939-6411(01)00165-5] [PMID: 11522482] 
[62] 
Scherphof, G.; Roerdink, F.; Waite, M.; Parks, J. Disintegration of phosphatidylcholine liposomes in plasma as a result of interaction with high-density lipoproteins. Biochim. Biophys. Acta,  1978, 542(2), 296-307.
[http://dx.doi.org/10.1016/0304-4165(78)90025-9] [PMID: 210837] 
[63] 
Patel, S.; Ashwanikumar, N.; Robinson, E.; Xia, Y.; Mihai, C.; Griffith, J.P., III; Hou, S.; Esposito, A.A.; Ketova, T.; Welsher, K.; Joyal, J.L.; Almarsson, Ö.; Sahay, G. Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA. Nat. Commun.,  2020, 11(1), 983.
[http://dx.doi.org/10.1038/s41467-020-14527-2] [PMID: 32080183] 
[64] 
Allen, T.M.; Hansen, C. Pharmacokinetics of stealth versus conventional liposomes: effect of dose. Biochim. Biophys. Acta,  1991, 1068(2), 133-141.
[http://dx.doi.org/10.1016/0005-2736(91)90201-I] [PMID: 1911826] 
[65] 
Kao, Y.J.; Juliano, R.L. Interactions of liposomes with the reticuloendothelial system. Effects of reticuloendothelial blockade on the clearance of large unilamellar vesicles. Biochim. Biophys. Acta,  1981, 677(3-4), 453-461.
[http://dx.doi.org/10.1016/0304-4165(81)90259-2] [PMID: 6895332] 
[66] 
Allen, T.M.; Chonn, A. Large unilamellar liposomes with low uptake into the reticuloendothelial system. FEBS Lett.,  1987, 223(1), 42-46.
[http://dx.doi.org/10.1016/0014-5793(87)80506-9] [PMID: 3666140] 
[67] 
Klibanov, A.L.; Maruyama, K.; Torchilin, V.P.; Huang, L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett.,  1990, 268(1), 235-237.
[http://dx.doi.org/10.1016/0014-5793(90)81016-H] [PMID: 2384160] 
[68] 
Blume, G.; Cevc, G. Liposomes for the sustained drug release in Vivo. Biochimica et Biophysica Acta (BBA) -. Biomembranes,  1990, 1029, 91-97.
[http://dx.doi.org/10.1016/0005-2736(90)90440-Y] 
[69] 
Jokerst, J.V.; Lobovkina, T.; Zare, R.N.; Gambhir, S.S. Nanoparticle PEGylation for imaging and therapy. Nanomedicine (Lond.),  2011, 6(4), 715-728.
[http://dx.doi.org/10.2217/nnm.11.19] [PMID: 21718180] 
[70] 
Suk, J.S.; Xu, Q.; Kim, N.; Hanes, J.; Ensign, L.M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery.Adv. Drug Deliv. Rev.,,  2016, 99(Pt A), 28-51..
[http://dx.doi.org/10.1016/j.addr.2015.09.012] [PMID: 26456916] 
[71] 
Ryals, R.C.; Patel, S.; Acosta, C.; McKinney, M.; Pennesi, M.E.; Sahay, G. The effects of PEGylation on LNP based mRNA delivery to the eye. PLoS One,  2020, 15(10)e0241006
[http://dx.doi.org/10.1371/journal.pone.0241006] [PMID: 33119640] 
[72] 
Kohli, A.G.; Kierstead, P.H.; Venditto, V.J.; Walsh, C.L.; Szoka, F.C. Designer lipids for drug delivery: from heads to tails. J. Control. Release,  2014, 190, 274-287.
[http://dx.doi.org/10.1016/j.jconrel.2014.04.047] [PMID: 24816069] 
[73] 
Mahon, K.P.; Love, K.T.; Whitehead, K.A.; Qin, J.; Akinc, A.; Leshchiner, E.; Leshchiner, I.; Langer, R.; Anderson, D.G. Combinatorial approach to determine functional group effects on lipidoid-mediated siRNA delivery. Bioconjug. Chem.,  2010, 21(8), 1448-1454.
[http://dx.doi.org/10.1021/bc100041r] [PMID: 20715849] 
[74] 
Love, K.T.; Mahon, K.P.; Levins, C.G.; Whitehead, K.A.; Querbes, W.; Dorkin, J.R.; Qin, J.; Cantley, W.; Qin, L.L.; Racie, T.; Frank-Kamenetsky, M.; Yip, K.N.; Alvarez, R.; Sah, D.W.Y.; de Fougerolles, A.; Fitzgerald, K.; Koteliansky, V.; Akinc, A.; Langer, R.; Anderson, D.G. Lipid-like materials for low-dose, in vivo gene silencing. Proc. Natl. Acad. Sci. USA,  2010, 107(5), 1864-1869.
[http://dx.doi.org/10.1073/pnas.0910603106] [PMID: 20080679] 
[75] 
Dong, Y.; Love, K.T.; Dorkin, J.R.; Sirirungruang, S.; Zhang, Y.; Chen, D.; Bogorad, R.L.; Yin, H.; Chen, Y.; Vegas, A.J.; Alabi, C.A.; Sahay, G.; Olejnik, K.T.; Wang, W.; Schroeder, A.; Lytton-Jean, A.K.R.; Siegwart, D.J.; Akinc, A.; Barnes, C.; Barros, S.A.; Carioto, M.; Fitzgerald, K.; Hettinger, J.; Kumar, V.; Novobrantseva, T.I.; Qin, J.; Querbes, W.; Koteliansky, V.; Langer, R.; Anderson, D.G. Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates. Proc. Natl. Acad. Sci. USA,  2014, 111(11), 3955-3960.
[http://dx.doi.org/10.1073/pnas.1322937111] [PMID: 24516150] 
[76] 
Dong, Y.; Siegwart, D.J.; Anderson, D.G. Strategies, design, and chemistry in siRNA delivery systems. Adv. Drug Deliv. Rev.,  2019, 144, 133-147.
[http://dx.doi.org/10.1016/j.addr.2019.05.004] [PMID: 31102606] 
[77] 
Sanna, V.; Caria, G.; Mariani, A. Effect of lipid nanoparticles containing fatty alcohols having different chain length on the ex vivo skin permeability of econazole nitrate. Powder Technol.,  2010, 201, 32-36.
[http://dx.doi.org/10.1016/j.powtec.2010.02.035] 
[78] 
Wang, M.; Sun, S.; Alberti, K.A.; Xu, Q. A combinatorial library of unsaturated lipidoids for efficient intracellular gene delivery. ACS Synth. Biol.,  2012, 1(9), 403-407.
[http://dx.doi.org/10.1021/sb300023h] [PMID: 23651337] 
[79] 
Altınoglu, S.; Wang, M.; Xu, Q. Combinatorial library strategies for synthesis of cationic lipid-like nanoparticles and their potential medical applications. Nanomedicine (Lond.),  2015, 10(4), 643-657.
[http://dx.doi.org/10.2217/nnm.14.192] [PMID: 25723096] 
[80] 
Hao, J.; Kos, P.; Zhou, K.; Miller, J.B.; Xue, L.; Yan, Y.; Xiong, H.; Elkassih, S.; Siegwart, D.J. Rapid synthesis of a lipocationic polyester library via ring-opening polymerization of functional valerolactones for efficacious sirna delivery. J. Am. Chem. Soc.,  2015, 137(29), 9206-9209.
[http://dx.doi.org/10.1021/jacs.5b03429] [PMID: 26166403] 
[81] 
Zhang, X.; Li, B.; Luo, X.; Zhao, W.; Jiang, J.; Zhang, C.; Gao, M.; Chen, X.; Dong, Y. Biodegradable amino-ester nanomaterials for cas9 mrna delivery in vitro and in vivo. ACS Appl. Mater. Interfaces,  2017, 9(30), 25481-25487.
[http://dx.doi.org/10.1021/acsami.7b08163] [PMID: 28685575] 
[82] 
Ball, R.L.; Hajj, K.A.; Vizelman, J.; Bajaj, P.; Whitehead, K.A. Lipid nanoparticle formulations for enhanced co-delivery of sirna and mrna. Nano Lett.,  2018, 18(6), 3814-3822.
[http://dx.doi.org/10.1021/acs.nanolett.8b01101] [PMID: 29694050] 
[83] 
Hajj, K.A.; Ball, R.L.; Deluty, S.B.; Singh, S.R.; Strelkova, D.; Knapp, C.M.; Whitehead, K.A. Branched-tail lipid nanoparticles potently deliver mrna in vivo due to enhanced ionization at endosomal ph. Small,  2019, 15(6)e1805097
[http://dx.doi.org/10.1002/smll.201805097] [PMID: 30637934] 
[84] 
Zhang, X.; Zhao, W.; Nguyen, G.N.; Zhang, C.; Zeng, C.; Yan, J.; Du, S.; Hou, X.; Li, W.; Jiang, J.; Deng, B.; McComb, D.W.; Dorkin, R.; Shah, A.; Barrera, L.; Gregoire, F.; Singh, M.; Chen, D.; Sabatino, D.E.; Dong, Y. Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing. Sci. Adv.,  2020, 6(34)eabc2315
[http://dx.doi.org/10.1126/sciadv.abc2315] [PMID: 32937374] 
[85] 
Li, B.; Luo, X.; Deng, B.; Wang, J.; McComb, D.W.; Shi, Y.; Gaensler, K.M.L.; Tan, X.; Dunn, A.L.; Kerlin, B.A.; Dong, Y. An orthogonal array optimization of lipid-like nanoparticles for mrna delivery in vivo. Nano Lett.,  2015, 15(12), 8099-8107.
[http://dx.doi.org/10.1021/acs.nanolett.5b03528] [PMID: 26529392] 
[86] 
Hou, X.; Zhang, X.; Zhao, W.; Zeng, C.; Deng, B.; McComb, D.W.; Du, S.; Zhang, C.; Li, W.; Dong, Y. Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis. Nat. Nanotechnol.,  2020, 15(1), 41-46.
[http://dx.doi.org/10.1038/s41565-019-0600-1] [PMID: 31907443] 
[87] 
Kauffman, K.J.; Dorkin, J.R.; Yang, J.H.; Heartlein, M.W.; DeRosa, F.; Mir, F.F.; Fenton, O.S.; Anderson, D.G. Optimization of lipid nanoparticle formulations for mrna delivery in vivo with fractional factorial and definitive screening designs. Nano Lett.,  2015, 15(11), 7300-7306.
[http://dx.doi.org/10.1021/acs.nanolett.5b02497] [PMID: 26469188] 
[88] 
Cheng, Q.; Wei, T.; Jia, Y.; Farbiak, L.; Zhou, K.; Zhang, S.; Wei, Y.; Zhu, H.; Siegwart, D.J. Dendrimer-based lipid nanoparticles deliver therapeutic fah mrna to normalize liver function and extend survival in a mouse model of hepatorenal tyrosinemia Type I. Adv. Mater.,  2018, 30(52)e1805308
[http://dx.doi.org/10.1002/adma.201805308] [PMID: 30368954] 
[89] 
Whitehead, K.A.; Dorkin, J.R.; Vegas, A.J.; Chang, P.H.; Veiseh, O.; Matthews, J.; Fenton, O.S.; Zhang, Y.; Olejnik, K.T.; Yesilyurt, V.; Chen, D.; Barros, S.; Klebanov, B.; Novobrantseva, T.; Langer, R.; Anderson, D.G. Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity. Nat. Commun.,  2014, 5, 4277.
[http://dx.doi.org/10.1038/ncomms5277] [PMID: 24969323] 
[90] 
Kulkarni, J.A.; Witzigmann, D.; Chen, S.; Cullis, P.R.; van der Meel, R. Lipid nanoparticle technology for clinical translation of sirna therapeutics. Acc. Chem. Res.,  2019, 52(9), 2435-2444.
[http://dx.doi.org/10.1021/acs.accounts.9b00368] [PMID: 31397996] 
[91] 
Szoka, F., Jr; Papahadjopoulos, D. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc. Natl. Acad. Sci. USA,  1978, 75(9), 4194-4198.
[http://dx.doi.org/10.1073/pnas.75.9.4194] [PMID: 279908] 
[92] 
Brunner, J.; Skrabal, P.; Hauser, H. Single bilayer vesicles prepared without sonication. Physico-chemical properties. Biochim. Biophys. Acta,  1976, 455(2), 322-331.
[http://dx.doi.org/10.1016/0005-2736(76)90308-4] [PMID: 1033769] 
[93] 
Bangham, A.; De Gier, J.; Greville, G. Osmotic properties and water permeability of phospholipid liquid crystals. Chem. Phys. Lipids,  1967, 1, 225-246.
[http://dx.doi.org/10.1016/0009-3084(67)90030-8] 
[94] 
Barenholzt, Y.; Amselem, S.; Lichtenberg, D. A new method for preparation of phospholipid vesicles (liposomes) - French press. FEBS Lett.,  1979, 99(1), 210-214.
[http://dx.doi.org/10.1016/0014-5793(79)80281-1] [PMID: 437128] 
[95] 
Pick, U. Liposomes with a large trapping capacity prepared by freezing and thawing of sonicated phospholipid mixtures. Arch. Biochem. Biophys.,  1981, 212(1), 186-194.
[http://dx.doi.org/10.1016/0003-9861(81)90358-1] [PMID: 7197900] 
[96] 
Magnan, C.; Badens, E.; Commenges, N.; Charbit, G. Soy lecithin micronization by precipitation with a compressed fluid antisolvent — influence of process parameters. J. Supercrit. Fluids,  2000, 19, 69-77.
[http://dx.doi.org/10.1016/S0896-8446(00)00076-0] 
[97] 
El-Ali, J.; Sorger, P.K.; Jensen, K.F. Cells on chips. Nature,  2006, 442(7101), 403-411.
[http://dx.doi.org/10.1038/nature05063] [PMID: 16871208] 
[98] 
Yager, P.; Edwards, T.; Fu, E.; Helton, K.; Nelson, K.; Tam, M.R.; Weigl, B.H. Microfluidic diagnostic technologies for global public health. Nature,  2006, 442(7101), 412-418.
[http://dx.doi.org/10.1038/nature05064] [PMID: 16871209] 
[99] 
Yu, B.; Lee, R.J.; Lee, L.J. Chapter 7 - Microfluidic Methods for Production of Liposomes. In: Methods in Enzymology; Methods in Enzymology; Academic Press: London, , 2009; 465, pp. 129-141.
[100] 
Leung, A.K.K.; Tam, Y.Y.C.; Chen, S.; Hafez, I.M.; Cullis, P.R. Microfluidic mixing: a general method for encapsulating macromolecules in lipid nanoparticle systems. J. Phys. Chem. B,  2015, 119(28), 8698-8706.
[http://dx.doi.org/10.1021/acs.jpcb.5b02891] [PMID: 26087393] 
[101] 
Kim, M.S.; Kim, J.S.; Park, H.J.; Cho, W.K.; Cha, K-H.; Hwang, S-J. Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process. Int. J. Nanomedicine,  2011, 6, 2997-3009.
[PMID: 22162657] 
[102] 
Otake, K.; Imura, T.; Sakai, H.; Abe, M. Development of a new preparation method of liposomes using supercritical carbon dioxide. langmuir, 2001, 17, 3898-3901.
[103] 
Otake, K.; Shimomura, T.; Goto, T.; Imura, T.; Furuya, T.; Yoda, S.; Takebayashi, Y.; Sakai, H.; Abe, M. Preparation of liposomes using an improved supercritical reverse phase evaporation method. Langmuir,  2006, 22(6), 2543-2550.
[http://dx.doi.org/10.1021/la051654u] [PMID: 16519453] 
[104] 
Otake, K.; Shimomura, T.; Goto, T.; Imura, T.; Furuya, T.; Yoda, S.; Takebayashi, Y.; Sakai, H.; Abe, M. One-step preparation of chitosan-coated cationic liposomes by an improved supercritical reverse-phase evaporation method. Langmuir,  2006, 22(9), 4054-4059.
[http://dx.doi.org/10.1021/la051662a] [PMID: 16618144] 
[105] 
Batzri, S.; Korn, E.D. Single bilayer liposomes prepared without sonication. Biochimica et Biophysica Acta (BBA)-. Biomembranes,  1973, 298, 1015-1019.
[http://dx.doi.org/10.1016/0005-2736(73)90408-2] 
[106] 
Deamer, D.; Bangham, A. Large volume liposomes by an ether vaporization method. Biochimica et Biophysica Acta (BBA)-. Biomembranes,  1976, 443, 629-634.
[http://dx.doi.org/10.1016/0005-2736(76)90483-1] 
[107] 
Kremer, J.M.; Esker, M.W.; Pathmamanoharan, C.; Wiersema, P.H. Vesicles of variable diameter prepared by a modified injection method. Biochemistry,  1977, 16(17), 3932-3935.
[http://dx.doi.org/10.1021/bi00636a033] [PMID: 901761] 
[108] 
Jaafar-Maalej, C.; Charcosset, C.; Fessi, H. A new method for liposome preparation using a membrane contactor. J. Liposome Res.,  2011, 21(3), 213-220.
[http://dx.doi.org/10.3109/08982104.2010.517537] [PMID: 20860451] 
[109] 
Laouini, A.; Jaafar-Maalej, C.; Sfar, S.; Charcosset, C.; Fessi, H. Liposome preparation using a hollow fiber membrane contactor--application to spironolactone encapsulation. Int. J. Pharm.,  2011, 415(1-2), 53-61.
[http://dx.doi.org/10.1016/j.ijpharm.2011.05.034] [PMID: 21641982] 
[110] 
Pham, T.T.; Jaafar-Maalej, C.; Charcosset, C.; Fessi, H. Liposome and niosome preparation using a membrane contactor for scale-up. Colloids Surf. B Biointerfaces,  2012, 94, 15-21.
[http://dx.doi.org/10.1016/j.colsurfb.2011.12.036] [PMID: 22326648] 
[111] 
Jeffs, L.B.; Palmer, L.R.; Ambegia, E.G.; Giesbrecht, C.; Ewanick, S.; MacLachlan, I. A scalable, extrusion-free method for efficient liposomal encapsulation of plasmid DNA. Pharm. Res.,  2005, 22(3), 362-372.
[http://dx.doi.org/10.1007/s11095-004-1873-z] [PMID: 15835741] 
[112] 
Zhang, Y-P.; Reimer, D.L.; Zhang, G.; Lee, P.H.; Bally, M.B. Self-assembling DNA-lipid particles for gene transfer. Pharm. Res.,  1997, 14(2), 190-196.
[http://dx.doi.org/10.1023/A:1012000711033] [PMID: 9090708] 
[113] 
Wheeler, J.J.; Palmer, L.; Ossanlou, M.; MacLachlan, I.; Graham, R.W.; Zhang, Y.P.; Hope, M.J.; Scherrer, P.; Cullis, P.R. Stabilized plasmid-lipid particles: construction and characterization. Gene Ther.,  1999, 6(2), 271-281.
[http://dx.doi.org/10.1038/sj.gt.3300821] [PMID: 10435112] 
[114] 
Tam, P.; Monck, M.; Lee, D.; Ludkovski, O.; Leng, E.C.; Clow, K.; Stark, H.; Scherrer, P.; Graham, R.W.; Cullis, P.R. Stabilized plasmid-lipid particles for systemic gene therapy. Gene Ther.,  2000, 7(21), 1867-1874.
[http://dx.doi.org/10.1038/sj.gt.3301308] [PMID: 11110420] 
[115] 
Fenske, D.B.; MacLachlan, I.; Cullis, P.R. Stabilized plasmid-lipid particles: a systemic gene therapy vector. Methods Enzymol.,  2002, 346, 36-71.
[http://dx.doi.org/10.1016/S0076-6879(02)46048-X] [PMID: 11883080] 
[116] 
Belliveau, N.M.; Huft, J.; Lin, P.J.; Chen, S.; Leung, A.K.; Leaver, T.J.; Wild, A.W.; Lee, J.B.; Taylor, R.J.; Tam, Y.K.; Hansen, C.L.; Cullis, P.R. Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of sirna. Mol. Ther. Nucleic Acids,  2012, 1e37
[http://dx.doi.org/10.1038/mtna.2012.28] [PMID: 23344179] 
[117] 
Chen, D.; Love, K.T.; Chen, Y.; Eltoukhy, A.A.; Kastrup, C.; Sahay, G.; Jeon, A.; Dong, Y.; Whitehead, K.A.; Anderson, D.G. Rapid discovery of potent siRNA-containing lipid nanoparticles enabled by controlled microfluidic formulation. J. Am. Chem. Soc.,  2012, 134(16), 6948-6951.
[http://dx.doi.org/10.1021/ja301621z] [PMID: 22475086] 
[118] 
Li, B.; Dong, Y. Preparation and optimization of lipid-like nanoparticles for mrna delivery. Methods Mol. Biol.,  2017, 1632, 207-217.
[119] 
Li, Y.; Lee, R.J.; Huang, X.; Li, Y.; Lv, B.; Wang, T.; Qi, Y.; Hao, F.; Lu, J.; Meng, Q.; Teng, L.; Zhou, Y.; Xie, J.; Teng, L. Single-step microfluidic synthesis of transferrin-conjugated lipid nanoparticles for siRNA delivery. Nanomedicine (Lond.),  2017, 13(2), 371-381.
[http://dx.doi.org/10.1016/j.nano.2016.09.014] [PMID: 27720989] 
[120] 
Hood, R.R.; DeVoe, D.L. High-throughput continuous flow
 production of nanoscale liposomes by microfluidic vertical flow
	focusing. small, 2015, 11, 5790-5799.
[121] 
Akbarzadeh, A.; Rezaei-Sadabady, R.; Davaran, S.; Joo, S.W.; Zarghami, N.; Hanifehpour, Y.; Samiei, M.; Kouhi, M.; Nejati-Koshki, K. Liposome: classification, preparation, and applications. Nanoscale Res. Lett.,  2013, 8(1), 102.
[http://dx.doi.org/10.1186/1556-276X-8-102] [PMID: 23432972] 
[122] 
Hwang, S.H.; Maitani, Y.; Qi, X-R.; Takayama, K.; Nagai, T. Remote loading of diclofenac, insulin and fluorescein isothiocyanate labeled insulin into liposomes by pH and acetate gradient methods. Int. J. Pharm.,  1999, 179(1), 85-95.
[http://dx.doi.org/10.1016/S0378-5173(98)00392-5] [PMID: 10053205] 
[123] 
Gabizon, A.; Shiota, R.; Papahadjopoulos, D. Pharmacokinetics and tissue distribution of doxorubicin encapsulated in stable liposomes with long circulation times. J. Natl. Cancer Inst.,  1989, 81(19), 1484-1488.
[http://dx.doi.org/10.1093/jnci/81.19.1484] [PMID: 2778836] 
[124] 
Fenske, D.B.; Wong, K.F.; Maurer, E.; Maurer, N.; Leenhouts, J.M.; Boman, N.; Amankwa, L.; Cullis, P.R. Ionophore-mediated uptake of ciprofloxacin and vincristine into large unilamellar vesicles exhibiting transmembrane ion gradients. Biochim. Biophys. Acta,  1998, 1414(1-2), 188-204.
[http://dx.doi.org/10.1016/S0005-2736(98)00166-7] [PMID: 9804953] 
[125] 
Lasic, D.D.; Frederik, P.M.; Stuart, M.C.A.; Barenholz, Y.; McIntosh, T.J. Gelation of liposome interior. A novel method for drug encapsulation. FEBS Lett.,  1992, 312(2-3), 255-258.
[http://dx.doi.org/10.1016/0014-5793(92)80947-F] [PMID: 1426260] 
[126] 
Yu, J.; Zhou, S.; Li, J.; Wang, Y.; Su, Y.; Chi, D.; Wang, J.; Wang, X.; He, Z.; Lin, G.; Liu, D.; Wang, Y. Simple weak-acid derivatives of paclitaxel for remote loading into liposomes and improved therapeutic effects. RSC Advances,  2020, 10, 27676-27687.
[http://dx.doi.org/10.1039/D0RA03190A] 
[127] 
Ulrich, A.S. Biophysical aspects of using liposomes as delivery vehicles. Biosci. Rep.,  2002, 22(2), 129-150.
[http://dx.doi.org/10.1023/A:1020178304031] [PMID: 12428898] 
[128] 
Chen, S.; Tam, Y.Y.C.; Lin, P.J.C.; Sung, M.M.H.; Tam, Y.K.; Cullis, P.R. Influence of particle size on the in vivo potency of lipid nanoparticle formulations of siRNA. J. Control. Release,  2016, 235, 236-244.
[http://dx.doi.org/10.1016/j.jconrel.2016.05.059] [PMID: 27238441] 
[129] 
Carr, B.; Wright, M. Nanoparticle tracking analysis. Innov. Pharma. Tech.,  2008, 26, 38-40.
[130] 
Hoo, C.M.; Starostin, N.; West, P.; Mecartney, M.L. A comparison of atomic force microscopy (afm) and dynamic light scattering (dls) methods to characterize nanoparticle size distributions. J. Nanopart. Res.,  2008, 10, 89-96.
[http://dx.doi.org/10.1007/s11051-008-9435-7] 
[131] 
Wang, H-X.; Zuo, Z-Q.; Du, J-Z.; Wang, Y-C.; Sun, R.; Cao, Z-T.; Ye, X-D.; Wang, J-L.; Leong, K.W.; Wang, J. Surface charge critically affects tumor penetration and therapeutic efficacy of cancer nanomedicines. Nano Today,  2016, 11, 133-144.
[http://dx.doi.org/10.1016/j.nantod.2016.04.008] 
[132] 
Sousa, Â.; Almeida, A.M.; Faria, R.; Konate, K.; Boisguerin, P.; Queiroz, J.A.; Costa, D. Optimization of peptide-plasmid DNA vectors formulation for gene delivery in cancer therapy exploring design of experiments. Colloids Surf. B Biointerfaces,  2019, 183110417
[http://dx.doi.org/10.1016/j.colsurfb.2019.110417] [PMID: 31408780] 
[133] 
Hunter, R.J.; Midmore, B.R.; Zhang, H. Zeta potential of highly charged thin double-layer systems. J. Colloid Interface Sci.,  2001, 237(1), 147-149.
[http://dx.doi.org/10.1006/jcis.2001.7423] [PMID: 11334528] 
[134] 
Schlieper, P.; Medda, P.K.; Kaufmann, R. Drug-induced zeta potential changes in liposomes studied by laser Doppler spectroscopy. Biochim. Biophys. Acta,  1981, 644(2), 273-283.
[http://dx.doi.org/10.1016/0005-2736(81)90385-0] [PMID: 6114748] 
[135] 
Lin, P-C.; Lin, S.; Wang, P.C.; Sridhar, R. Techniques for physicochemical characterization of nanomaterials. Biotechnol. Adv.,  2014, 32(4), 711-726.
[http://dx.doi.org/10.1016/j.biotechadv.2013.11.006] [PMID: 24252561] 
[136] 
Kulkarni, J.A.; Darjuan, M.M.; Mercer, J.E.; Chen, S.; van der Meel, R.; Thewalt, J.L.; Tam, Y.Y.C.; Cullis, P.R. On the formation and morphology of lipid nanoparticles containing ionizable cationic lipids and siRNA. ACS Nano,  2018, 12(5), 4787-4795.
[http://dx.doi.org/10.1021/acsnano.8b01516] [PMID: 29614232] 
[137] 
Kuntsche, J.; Horst, J.C.; Bunjes, H. Cryogenic transmission electron microscopy (cryo-TEM) for studying the morphology of colloidal drug delivery systems. Int. J. Pharm.,  2011, 417(1-2), 120-137.
[http://dx.doi.org/10.1016/j.ijpharm.2011.02.001] [PMID: 21310225] 
[138] 
Lasic, D.D. Doxorubicin in sterically stabilized liposomes. Nature,  1996, 380(6574), 561-562.
[http://dx.doi.org/10.1038/380561a0] [PMID: 8606781] 
[139] 
Li, X.; Hirsh, D.J.; Cabral-Lilly, D.; Zirkel, A.; Gruner, S.M.; Janoff, A.S.; Perkins, W.R. Doxorubicin physical state in solution and inside liposomes loaded via a pH gradient. Biochim. Biophys. Acta,  1998, 1415(1), 23-40.
[http://dx.doi.org/10.1016/S0005-2736(98)00175-8] [PMID: 9858673] 
[140] 
Gilleron, J.; Querbes, W.; Zeigerer, A.; Borodovsky, A.; Marsico, G.; Schubert, U.; Manygoats, K.; Seifert, S.; Andree, C.; Stöter, M.; Epstein-Barash, H.; Zhang, L.; Koteliansky, V.; Fitzgerald, K.; Fava, E.; Bickle, M.; Kalaidzidis, Y.; Akinc, A.; Maier, M.; Zerial, M. Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat. Biotechnol.,  2013, 31(7), 638-646.
[http://dx.doi.org/10.1038/nbt.2612] [PMID: 23792630] 
[141] 
Liu, C.; Zhao, G.; Liu, J.; Ma, N.; Chivukula, P.; Perelman, L.; Okada, K.; Chen, Z.; Gough, D.; Yu, L. Novel biodegradable lipid nano complex for siRNA delivery significantly improving the chemosensitivity of human colon cancer stem cells to paclitaxel. J. Control. Release,  2009, 140(3), 277-283.
[http://dx.doi.org/10.1016/j.jconrel.2009.08.013] [PMID: 19699770] 
[142] 
Li, J.; Chen, Y-C.; Tseng, Y-C.; Mozumdar, S.; Huang, L. Biodegradable calcium phosphate nanoparticle with lipid coating for systemic siRNA delivery. J. Control. Release,  2010, 142(3), 416-421.
[http://dx.doi.org/10.1016/j.jconrel.2009.11.008] [PMID: 19919845] 
[143] 
Billingsley, M.M.; Singh, N.; Ravikumar, P.; Zhang, R.; June, C.H.; Mitchell, M.J. Ionizable lipid nanoparticle-mediated mrna delivery for human car t cell engineering. Nano Lett.,  2020, 20(3), 1578-1589.
[http://dx.doi.org/10.1021/acs.nanolett.9b04246] [PMID: 31951421] 
[144] 
Patel, S.; Ashwanikumar, N.; Robinson, E.; DuRoss, A.; Sun, C.; Murphy-Benenato, K.E.; Mihai, C.; Almarsson, Ö.; Sahay, G. Boosting intracellular delivery of lipid nanoparticle-encapsulated mrna. Nano Lett.,  2017, 17(9), 5711-5718.
[http://dx.doi.org/10.1021/acs.nanolett.7b02664] [PMID: 28836442] 
[145] 
Kaczmarek, J.C.; Kauffman, K.J.; Fenton, O.S.; Sadtler, K.; Patel, A.K.; Heartlein, M.W.; DeRosa, F.; Anderson, D.G. Optimization of a degradable polymer-lipid nanoparticle for potent systemic delivery of mrna to the lung endothelium and immune cells. Nano Lett.,  2018, 18(10), 6449-6454.
[http://dx.doi.org/10.1021/acs.nanolett.8b02917] [PMID: 30211557] 
[146] 
Zhao, W.; Zhang, C.; Li, B.; Zhang, X.; Luo, X.; Zeng, C.; Li, W.; Gao, M.; Dong, Y. Lipid polymer hybrid nanomaterials for mrna delivery. Cell. Mol. Bioeng.,  2018, 11(5), 397-406.
[http://dx.doi.org/10.1007/s12195-018-0536-9] [PMID: 30555598] 
[147] 
Yu, X.; Liu, S.; Cheng, Q.; Wei, T.; Lee, S.; Zhang, D.; Siegwart, D.J. Lipid-Modified Aminoglycosides for mRNA Delivery to the Liver. Adv. Healthc. Mater.,  2020, 9(7)e1901487
[http://dx.doi.org/10.1002/adhm.201901487] [PMID: 32108440] 
[148] 
Jiang, T.; Xing, B.; Rao, J. Recent developments of biological reporter technology for detecting gene expression. Biotechnol. Genet. Eng. Rev.,  2008, 25, 41-75.
[http://dx.doi.org/10.5661/bger-25-41] [PMID: 21412349] 
[149] 
Whitehead, K.A.; Matthews, J.; Chang, P.H.; Niroui, F.; Dorkin, J.R.; Severgnini, M.; Anderson, D.G. In vitro-in vivo translation of lipid nanoparticles for hepatocellular siRNA delivery. ACS Nano,  2012, 6(8), 6922-6929.
[http://dx.doi.org/10.1021/nn301922x] [PMID: 22770391] 
[150] 
Lokugamage, M.P.; Sago, C.D.; Dahlman, J.E. Testing thousands of nanoparticles in vivo using DNA barcodes. Curr Opin Biomed Eng,  2018, 7, 1-8.
[http://dx.doi.org/10.1016/j.cobme.2018.08.001] [PMID: 30931416] 
[151] 
Paunovska, K.; Da Silva Sanchez, A.J.; Sago, C.D.; Gan, Z.; Lokugamage, M.P.; Islam, F.Z.; Kalathoor, S.; Krupczak, B.R.; Dahlman, J.E. Nanoparticles containing oxidized cholesterol deliver mrna to the liver microenvironment at clinically relevant doses. Adv. Mater.,  2019, 31(14)e1807748
[http://dx.doi.org/10.1002/adma.201807748] [PMID: 30748040] 
[152] 
Sago, C.D.; Lokugamage, M.P.; Paunovska, K.; Vanover, D.A.; Monaco, C.M.; Shah, N.N.; Gamboa Castro, M.; Anderson, S.E.; Rudoltz, T.G.; Lando, G.N.; Munnilal Tiwari, P.; Kirschman, J.L.; Willett, N.; Jang, Y.C.; Santangelo, P.J.; Bryksin, A.V.; Dahlman, J.E. High-throughput in vivo screen of functional mRNA delivery identifies nanoparticles for endothelial cell gene editing. Proc. Natl. Acad. Sci. USA,  2018, 115(42), E9944-E9952.
[http://dx.doi.org/10.1073/pnas.1811276115] [PMID: 30275336] 
[153] 
Dahlman, J.E.; Kauffman, K.J.; Xing, Y.; Shaw, T.E.; Mir, F.F.; Dlott, C.C.; Langer, R.; Anderson, D.G.; Wang, E.T. Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics. Proc. Natl. Acad. Sci. USA,  2017, 114(8), 2060-2065.
[http://dx.doi.org/10.1073/pnas.1620874114] [PMID: 28167778] 
[154] 
Guimaraes, P.P.G.; Zhang, R.; Spektor, R.; Tan, M.; Chung, A.; Billingsley, M.M.; El-Mayta, R.; Riley, R.S.; Wang, L.; Wilson, J.M.; Mitchell, M.J. Ionizable lipid nanoparticles encapsulating barcoded mRNA for accelerated in vivo delivery screening. J. Control. Release,  2019, 316, 404-417.
[http://dx.doi.org/10.1016/j.jconrel.2019.10.028] [PMID: 31678653] 
[155] 
Frenkel, D.; Smit, B. Understanding molecular simulation: From algorithms to applications; Academic Press: London, 2001. 
[156] 
Gooneie, A.; Schuschnigg, S.; Holzer, C. A Review of Multiscale Computational Methods in Polymeric Materials. Polymers (Basel),  2017, 9(1), 16.
[http://dx.doi.org/10.3390/polym9010016] [PMID: 30970697] 
[157] 
Sherwood, P.; Brooks, B.R.; Sansom, M.S. Multiscale methods for macromolecular simulations. Curr. Opin. Struct. Biol.,  2008, 18(5), 630-640.
[http://dx.doi.org/10.1016/j.sbi.2008.07.003] [PMID: 18721882] 
[158] 
Meier, K.; Choutko, A.; Dolenc, J.; Eichenberger, A.P.; Riniker, S.; van Gunsteren, W.F. Multi-resolution simulation of biomolecular systems: a review of methodological issues. Angew. Chem. Int. Ed. Engl.,  2013, 52(10), 2820-2834.
[http://dx.doi.org/10.1002/anie.201205408] [PMID: 23417997] 
[159] 
Dickson, C.J.; Madej, B.D.; Skjevik, Å.A.; Betz, R.M.; Teigen, K.; Gould, I.R.; Walker, R.C. Lipid14: The amber lipid force field. J. Chem. Theory Comput.,  2014, 10(2), 865-879.
[http://dx.doi.org/10.1021/ct4010307] [PMID: 24803855] 
[160] 
Huang, J.; Rauscher, S.; Nawrocki, G.; Ran, T.; Feig, M.; de Groot, B.L.; Grubmüller, H.; MacKerell, A.D., Jr CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nat. Methods,  2017, 14(1), 71-73.
[http://dx.doi.org/10.1038/nmeth.4067] [PMID: 27819658] 
[161] 
Klauda, J.B.; Venable, R.M.; Freites, J.A.; O’Connor, J.W.; Tobias, D.J.; Mondragon-Ramirez, C.; Vorobyov, I.; MacKerell, A.D., Jr; Pastor, R.W. Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J. Phys. Chem. B,  2010, 114(23), 7830-7843.
[http://dx.doi.org/10.1021/jp101759q] [PMID: 20496934] 
[162] 
Hart, K.; Foloppe, N.; Baker, C.M.; Denning, E.J.; Nilsson, L.; Mackerell, A.D., Jr Optimization of the CHARMM additive force field for DNA: Improved treatment of the BI/BII conformational equilibrium. J. Chem. Theory Comput.,  2012, 8(1), 348-362.
[http://dx.doi.org/10.1021/ct200723y] [PMID: 22368531] 
[163] 
Denning, E.J.; Priyakumar, U.D.; Nilsson, L.; Mackerell, A.D. Jr Impact of 2′-hydroxyl sampling on the conformational properties of RNA: update of the CHARMM all-atom additive force field for RNA. J. Comput. Chem.,  2011, 32(9), 1929-1943.
[http://dx.doi.org/10.1002/jcc.21777] [PMID: 21469161] 
[164] 
Siu, S.W.I.; Pluhackova, K.; Böckmann, R.A. Optimization of the opls-aa force field for long hydrocarbons. J. Chem. Theory Comput.,  2012, 8(4), 1459-1470.
[http://dx.doi.org/10.1021/ct200908r] [PMID: 26596756] 
[165] 
Sun, D.; Forsman, J.; Woodward, C.E. Evaluating force fields for the computational prediction of ionized arginine and lysine side-chains partitioning into lipid bilayers and octanol. J. Chem. Theory Comput.,  2015, 11(4), 1775-1791.
[http://dx.doi.org/10.1021/ct501063a] [PMID: 26574387] 
[166] 
Best, R.B.; Hofmann, H.; Nettels, D.; Schuler, B. Quantitative interpretation of FRET experiments via molecular simulation: force field and validation. Biophys. J.,  2015, 108(11), 2721-2731.
[http://dx.doi.org/10.1016/j.bpj.2015.04.038] [PMID: 26039173] 
[167] 
Brooks, B.R.; Brooks, C.L., III; Mackerell, A.D., Jr; Nilsson, L.; Petrella, R.J.; Roux, B.; Won, Y.; Archontis, G.; Bartels, C.; Boresch, S.; Caflisch, A.; Caves, L.; Cui, Q.; Dinner, A.R.; Feig, M.; Fischer, S.; Gao, J.; Hodoscek, M. Im, W.; Kuczera, K.; Lazaridis, T.; Ma, J.; Ovchinnikov, V.; Paci, E.; Pastor, R.W.; Post, C.B.; Pu, J.Z.; Schaefer, M.; Tidor, B.; Venable, R.M.; Woodcock, H.L.; Wu, X.; Yang, W.; York, D.M.; Karplus, M. CHARMM: the biomolecular simulation program. J. Comput. Chem.,  2009, 30(10), 1545-1614.
[http://dx.doi.org/10.1002/jcc.21287] [PMID: 19444816] 
[168] 
Case, D.A.; Cheatham, T.E., III; Darden, T.; Gohlke, H.; Luo, R.; Merz, K.M., Jr; Onufriev, A.; Simmerling, C.; Wang, B.; Woods, R.J. The Amber biomolecular simulation programs. J. Comput. Chem.,  2005, 26(16), 1668-1688.
[http://dx.doi.org/10.1002/jcc.20290] [PMID: 16200636] 
[169] 
Phillips, J.C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.; Skeel, R.D.; Kalé, L.; Schulten, K. Scalable molecular dynamics with NAMD. J. Comput. Chem.,  2005, 26(16), 1781-1802.
[http://dx.doi.org/10.1002/jcc.20289] [PMID: 16222654] 
[170] 
Abraham, M.J.; Murtola, T.; Schulz, R.; Páll, S.; Smith, J.C.; Hess, B.; Lindahl, E. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX,  2015, 1-2, 19-25.
[http://dx.doi.org/10.1016/j.softx.2015.06.001] 
[171] 
Eastman, P.; Swails, J.; Chodera, J.D.; McGibbon, R.T.; Zhao, Y.; Beauchamp, K.A.; Wang, L-P.; Simmonett, A.C.; Harrigan, M.P.; Stern, C.D.; Wiewiora, R.P.; Brooks, B.R.; Pande, V.S. OpenMM 7: Rapid development of high performance algorithms for molecular dynamics. PLOS Comput. Biol.,  2017, 13(7)e1005659
[http://dx.doi.org/10.1371/journal.pcbi.1005659] [PMID: 28746339] 
[172] 
Plimpton, S. Fast parallel algorithms for short-range molecular dynamics. J. Comput. Phys.,  1995, 117, 1-19.
[http://dx.doi.org/10.1006/jcph.1995.1039] 
[173] 
Marrink, S.J.; Tieleman, D.P. Perspective on the martini model. Chem. Soc. Rev.,  2013, 42(16), 6801-6822.
[http://dx.doi.org/10.1039/c3cs60093a] [PMID: 23708257] 
[174] 
Pak, A.J.; Voth, G.A. Advances in coarse-grained modeling of macromolecular complexes. Curr. Opin. Struct. Biol.,  2018, 52, 119-126.
[http://dx.doi.org/10.1016/j.sbi.2018.11.005] [PMID: 30508766] 
[175] 
Lu, L.; Dama, J.F.; Voth, G.A. Fitting coarse-grained distribution functions through an iterative force-matching method. J. Chem. Phys.,  2013, 139(12)121906
[http://dx.doi.org/10.1063/1.4811667] [PMID: 24089718] 
[176] 
Izvekov, S.; Voth, G.A. Effective force field for liquid hydrogen fluoride from ab initio molecular dynamics simulation using the force-matching method. J. Phys. Chem. B,  2005, 109(14), 6573-6586.
[http://dx.doi.org/10.1021/jp0456685] [PMID: 16851738] 
[177] 
Lyman, E.; Pfaendtner, J.; Voth, G.A. Systematic multiscale parameterization of heterogeneous elastic network models of proteins. Biophys. J.,  2008, 95(9), 4183-4192.
[http://dx.doi.org/10.1529/biophysj.108.139733] [PMID: 18658214] 
[178] 
Lu, L.; Voth, G.A. Systematic coarse-graining of a multicomponent lipid bilayer. J. Phys. Chem. B,  2009, 113(5), 1501-1510.
[http://dx.doi.org/10.1021/jp809604k] [PMID: 19138138] 
[179] 
Izvekov, S.; Voth, G.A. Solvent-free lipid bilayer model using multiscale coarse-graining. J. Phys. Chem. B,  2009, 113(13), 4443-4455.
[http://dx.doi.org/10.1021/jp810440c] [PMID: 19267467] 
[180] 
Chu, J-W.; Izveko, S.; Voth, G.A. The multiscale challenge for biomolecular systems: coarse-grained modeling. Mol. Simul.,  2006, 32, 211-218.
[http://dx.doi.org/10.1080/08927020600612221] 
[181] 
Grime, J.M.A.; Dama, J.F.; Ganser-Pornillos, B.K.; Woodward, C.L.; Jensen, G.J.; Yeager, M.; Voth, G.A. Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly. Nat. Commun.,  2016, 7, 11568.
[http://dx.doi.org/10.1038/ncomms11568] [PMID: 27174390] 
[182] 
Noguchi, H.; Takasu, M. Adhesion of nanoparticles to vesicles: a Brownian dynamics simulation. Biophys. J.,  2002, 83(1), 299-308.
[http://dx.doi.org/10.1016/S0006-3495(02)75170-9] [PMID: 12080121] 
[183] 
Noguchi, H.; Takasu, M. Structural changes of pulled vesicles: a Brownian dynamics simulation. Phys. Rev. E Stat. Nonlin. Soft Matter Phys.,  2002, 65(5 Pt 1)051907
[http://dx.doi.org/10.1103/PhysRevE.65.051907] [PMID: 12059593] 
[184] 
Goga, N.; Rzepiela, A.J.; de Vries, A.H.; Marrink, S.J.; Berendsen, H.J.C. Efficient algorithms for langevin and dpd dynamics. J. Chem. Theory Comput.,  2012, 8(10), 3637-3649.
[http://dx.doi.org/10.1021/ct3000876] [PMID: 26593009] 
[185] 
Moeendarbary, E.; Ng, T.Y.; Zangeneh, M. Dissipative particle dynamics: introduction, methodology and complex fluid applications — a review. Int. J. Appl. Mech.,  2009, 01, 737-763.
[http://dx.doi.org/10.1142/S1758825109000381] 
[186] 
Sadeghi, M.; Noé, F. Large-scale simulation of biomembranes incorporating realistic kinetics into coarse-grained models. Nat. Commun.,  2020, 11(1), 2951.
[http://dx.doi.org/10.1038/s41467-020-16424-0] [PMID: 32528158] 
[187] 
Pezeshkian, W.; König, M.; Wassenaar, T.A.; Marrink, S.J. Backmapping triangulated surfaces to coarse-grained membrane models. Nat. Commun.,  2020, 11(1), 2296.
[http://dx.doi.org/10.1038/s41467-020-16094-y] [PMID: 32385270] 
[188] 
Simunovic, M.; Evergren, E.; Golushko, I.; Prévost, C.; Renard, H-F.; Johannes, L.; McMahon, H.T.; Lorman, V.; Voth, G.A.; Bassereau, P. How curvature-generating proteins build scaffolds on membrane nanotubes. Proc. Natl. Acad. Sci. USA,  2016, 113(40), 11226-11231.
[http://dx.doi.org/10.1073/pnas.1606943113] [PMID: 27655892] 
[189] 
Davtyan, A.; Simunovic, M.; Voth, G.A. The mesoscopic membrane with proteins (MesM-P) model. J. Chem. Phys.,  2017, 147(4)044101
[http://dx.doi.org/10.1063/1.4993514] [PMID: 28764362] 
[190] 
Bahrami, A.H.; Lipowsky, R.; Weikl, T.R. Tubulation and aggregation of spherical nanoparticles adsorbed on vesicles. Phys. Rev. Lett.,  2012, 109(18)188102
[http://dx.doi.org/10.1103/PhysRevLett.109.188102] [PMID: 23215335] 
[191] 
Hoore, M.; Yaya, F.; Podgorski, T.; Wagner, C.; Gompper, G.; Fedosov, D.A. Effect of spectrin network elasticity on the shapes of erythrocyte doublets. Soft Matter,  2018, 14(30), 6278-6289.
[http://dx.doi.org/10.1039/C8SM00634B] [PMID: 30014074] 
[192] 
Cournia, Z.; Ullmann, G.M.; Smith, J.C. Differential effects of cholesterol, ergosterol and lanosterol on a dipalmitoyl phosphatidylcholine membrane: a molecular dynamics simulation study. J. Phys. Chem. B,  2007, 111(7), 1786-1801.
[http://dx.doi.org/10.1021/jp065172i] [PMID: 17261058] 
[193] 
Pan, J.; Cheng, X.; Heberle, F.A.; Mostofian, B.; Kučerka, N.; Drazba, P.; Katsaras, J. Interactions between ether phospholipids and cholesterol as determined by scattering and molecular dynamics simulations. J. Phys. Chem. B,  2012, 116(51), 14829-14838.
[http://dx.doi.org/10.1021/jp310345j] [PMID: 23199292] 
[194] 
Sodt, A.J.; Sandar, M.L.; Gawrisch, K.; Pastor, R.W.; Lyman, E. The molecular structure of the liquid-ordered phase of lipid bilayers. J. Am. Chem. Soc.,  2014, 136(2), 725-732.
[http://dx.doi.org/10.1021/ja4105667] [PMID: 24345334] 
[195] 
Johnson, Q.R.; Mostofian, B.; Fuente Gomez, G.; Smith, J.C.; Cheng, X. Effects of carotenoids on lipid bilayers. Phys. Chem. Chem. Phys.,  2018, 20(5), 3795-3804.
[http://dx.doi.org/10.1039/C7CP07126D] [PMID: 29349456] 
[196] 
Mostofian, B.; Johnson, Q.R.; Smith, J.C.; Cheng, X. Carotenoids promote lateral packing and condensation of lipid membranes. Phys. Chem. Chem. Phys.,  2020, 22(21), 12281-12293.
[http://dx.doi.org/10.1039/D0CP01031F] [PMID: 32432296] 
[197] 
McClements, D.J. Enhanced delivery of lipophilic bioactives using emulsions: a review of major factors affecting vitamin, nutraceutical, and lipid bioaccessibility. Food Funct.,  2018, 9(1), 22-41.
[http://dx.doi.org/10.1039/C7FO01515A] [PMID: 29119979] 
[198] 
Atkinson, J.; Harroun, T.; Wassall, S.R.; Stillwell, W.; Katsaras, J. The location and behavior of α-tocopherol in membranes. Mol. Nutr. Food Res.,  2010, 54(5), 641-651.
[http://dx.doi.org/10.1002/mnfr.200900439] [PMID: 20166146] 
[199] 
Cheng, X.; Smith, J.C. Biological membrane organization and cellular signaling. Chem. Rev.,  2019, 119(9), 5849-5880.
[http://dx.doi.org/10.1021/acs.chemrev.8b00439] [PMID: 30747526] 
[200] 
Merz, K.M., Jr Molecular dynamics simulations of lipid bilayers. Curr. Opin. Struct. Biol.,  1997, 7(4), 511-517.
[http://dx.doi.org/10.1016/S0959-440X(97)80115-7] [PMID: 9266172] 
[201] 
Merz, K.M.; Roux, B. Biological Membranes: A Molecular Perspective from Computation and Experiment; Springer Science & Business Media: Berlin, 2012. 
[202] 
Marrink, S-J.; Berendsen, H.J.C. Simulation of water transport through a lipid membrane. J. Phys. Chem.,  1994, 98, 4155-4168.
[http://dx.doi.org/10.1021/j100066a040] 
[203] 
Marrink, S.J.; Berendsen, H.J.C. Permeation process of small molecules across lipid membranes studied by molecular dynamics simulations. J. Phys. Chem.,  1996, 100, 16729-16738.
[http://dx.doi.org/10.1021/jp952956f] 
[204] 
Bemporad, D.; Luttmann, C.; Essex, J.W. Computer simulation of small molecule permeation across a lipid bilayer: dependence on bilayer properties and solute volume, size, and cross-sectional area. Biophys. J.,  2004, 87(1), 1-13.
[http://dx.doi.org/10.1529/biophysj.103.030601] [PMID: 15240439] 
[205] 
Bemporad, D.; Essex, J.W.; Luttmann, C. Permeation of small molecules through a lipid bilayer: a computer simulation study. J. Phys. Chem. B,  2004, 108, 4875-4884.
[http://dx.doi.org/10.1021/jp035260s] 
[206] 
Zhang, H.; Shao, X.; Dehez, F.; Cai, W.; Chipot, C. Modulation of membrane permeability by carbon dioxide. J. Comput. Chem.,  2020, 41(5), 421-426.
[http://dx.doi.org/10.1002/jcc.26063] [PMID: 31479166] 
[207] 
Comer, J.; Schulten, K.; Chipot, C. Permeability of a fluid lipid bilayer to short-chain alcohols from first principles. J. Chem. Theory Comput.,  2017, 13(6), 2523-2532.
[http://dx.doi.org/10.1021/acs.jctc.7b00264] 
[208] 
Chipot, C.; Comer, J. Subdiffusion in membrane permeation of small molecules. Sci. Rep.,  2016, 6, 35913.
[http://dx.doi.org/10.1038/srep35913] [PMID: 27805049] 
[209] 
Tse, C.H.; Comer, J.Sang; Chu,  S.K.; Wang, Y.; Chipot, C. Affordable membrane permeability calculations: permeation of short-chain alcohols through pure-lipid bilayers and a mammalian cell membrane. J. Chem. Theory Comput.,  2019, 15(5), 2913-2924.
[http://dx.doi.org/10.1021/acs.jctc.9b00022] [PMID: 30998342] 
[210] 
Comer, J.; Chipot, C.; González-Nilo, F.D. Calculating position-dependent diffusivity in biased molecular dynamics simulations. J. Chem. Theory Comput.,  2013, 9(2), 876-882.
[http://dx.doi.org/10.1021/ct300867e] [PMID: 26588731] 
[211] 
Comer, J.; Gumbart, J.C.; Hénin, J.; Lelièvre, T.; Pohorille, A.; Chipot, C. The adaptive biasing force method: everything you always wanted to know but were afraid to ask. J. Phys. Chem. B,  2014, 119(3), 1129-1151.
[212] 
Martinotti, C.; Ruiz-Perez, L.; Deplazes, E.; Mancera, R.L. Molecular dynamics simulation of the interaction of small molecules with biological membranes.ChemPhysChem,, 2020. ePub ahead of Print
[213] 
Venable, R.M.; Krämer, A.; Pastor, R.W. Molecular dynamics simulations of membrane permeability. Chem. Rev.,  2019, 119(9), 5954-5997.
[http://dx.doi.org/10.1021/acs.chemrev.8b00486] [PMID: 30747524] 
[214] 
Dzieciuch, M.; Rissanen, S.; Szydłowska, N.; Bunker, A.; Kumorek, M.; Jamróz, D.; Vattulainen, I.; Nowakowska, M.; Róg, T.; Kepczynski, M. PEGylated liposomes as carriers of hydrophobic porphyrins. J. Phys. Chem. B,  2015, 119(22), 6646-6657.
[http://dx.doi.org/10.1021/acs.jpcb.5b01351] [PMID: 25965670] 
[215] 
Lehtinen, J.; Magarkar, A.; Stepniewski, M.; Hakola, S.; Bergman, M.; Róg, T.; Yliperttula, M.; Urtti, A.; Bunker, A. Analysis of cause of failure of new targeting peptide in PEGylated liposome: molecular modeling as rational design tool for nanomedicine. Eur. J. Pharm. Sci.,  2012, 46(3), 121-130.
[http://dx.doi.org/10.1016/j.ejps.2012.02.009] [PMID: 22381076] 
[216] 
Li, Y-C.; Rissanen, S.; Stepniewski, M.; Cramariuc, O.; Róg, T.; Mirza, S.; Xhaard, H.; Wytrwal, M.; Kepczynski, M.; Bunker, A. Study of interaction between PEG carrier and three relevant drug molecules: piroxicam, paclitaxel, and hematoporphyrin. J. Phys. Chem. B,  2012, 116(24), 7334-7341.
[http://dx.doi.org/10.1021/jp300301z] [PMID: 22587534] 
[217] 
Vuković, L.; Khatib, F.A.; Drake, S.P.; Madriaga, A.; Brandenburg, K.S.; Král, P.; Onyuksel, H. Structure and dynamics of highly PEG-ylated sterically stabilized micelles in aqueous media. J. Am. Chem. Soc.,  2011, 133(34), 13481-13488.
[http://dx.doi.org/10.1021/ja204043b] [PMID: 21780810] 
[218] 
Vuković, L.; Madriaga, A.; Kuzmis, A.; Banerjee, A.; Tang, A.; Tao, K.; Shah, N.; Král, P.; Onyuksel, H. Solubilization of therapeutic agents in micellar nanomedicines. Langmuir,  2013, 29(51), 15747-15754.
[http://dx.doi.org/10.1021/la403264w] [PMID: 24283508] 
[219] 
Magarkar, A.; Róg, T.; Bunker, A. Molecular dynamics simulation of pegylated membranes with cholesterol: building toward the doxil formulation. J. Phys. Chem. C,  2014, 118, 15541-15549.
[http://dx.doi.org/10.1021/jp504962m] 
[220] 
Eriksson, E.S.E.; Eriksson, L.A. The influence of cholesterol on the properties and permeability of hypericin derivatives in lipid membranes. J. Chem. Theory Comput.,  2011, 7(3), 560-574.
[http://dx.doi.org/10.1021/ct100528u] [PMID: 26596290] 
[221] 
Khelashvili, G.; Harries, D. How cholesterol tilt modulates the mechanical properties of saturated and unsaturated lipid membranes. J. Phys. Chem. B,  2013, 117(8), 2411-2421.
[http://dx.doi.org/10.1021/jp3122006] [PMID: 23323733] 
[222] 
Magarkar, A.; Karakas, E.; Stepniewski, M.; Róg, T.; Bunker, A. Molecular dynamics simulation of PEGylated bilayer interacting with salt ions: a model of the liposome surface in the bloodstream. J. Phys. Chem. B,  2012, 116(14), 4212-4219.
[http://dx.doi.org/10.1021/jp300184z] [PMID: 22420691] 
[223] 
Stepniewski, M.; Pasenkiewicz-Gierula, M.; Róg, T.; Danne, R.; Orlowski, A.; Karttunen, M.; Urtti, A.; Yliperttula, M.; Vuorimaa, E.; Bunker, A. Study of PEGylated lipid layers as a model for PEGylated liposome surfaces: molecular dynamics simulation and Langmuir monolayer studies. Langmuir,  2011, 27(12), 7788-7798.
[http://dx.doi.org/10.1021/la200003n] [PMID: 21604684] 
[224] 
Bunker, A.; Magarkar, A.; Viitala, T. Rational design of liposomal drug delivery systems, a review: Combined experimental and computational studies of lipid membranes, liposomes and their PEGylation. Biochim. Biophys. Acta,  2016, 1858(10), 2334-2352.
[http://dx.doi.org/10.1016/j.bbamem.2016.02.025] [PMID: 26915693] 
[225] 
Nosova, A.S.; Koloskova, O.O.; Nikonova, A.A.; Simonova, V.A.; Smirnov, V.V.; Kudlay, D.; Khaitov, M.R. Diversity of PEGylation methods of liposomes and their influence on RNA delivery. MedChemComm,  2019, 10(3), 369-377.
[http://dx.doi.org/10.1039/C8MD00515J] [PMID: 31015904] 
[226] 
Sousa, S.F.; Peres, J.; Coelho, M.; Vieira, T.F. Analyzing pegylation through molecular dynamics simulations. ChemistrySelect,  2018, 3, 8415-8427.
[http://dx.doi.org/10.1002/slct.201800855] 
[227] 
Irby, D.; Du, C.; Li, F. Lipid-drug conjugate for enhancing drug delivery. Mol. Pharm.,  2017, 14(5), 1325-1338.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b01027] [PMID: 28080053] 
[228] 
Ramezanpour, M.; Leung, S.S.W.; Delgado-Magnero, K.H.; Bashe, B.Y.M.; Thewalt, J.; Tieleman, D.P. Computational and experimental approaches for investigating nanoparticle-based drug delivery systems. Biochim. Biophys. Acta,  2016, 1858(7 Pt B), 1688-1709.
[http://dx.doi.org/10.1016/j.bbamem.2016.02.028] [PMID: 26930298] 
[229] 
Wang, P.; Ma, Y.; Liu, Z.; Yan, Y.; Sun, X.; Zhang, J. Vesicle formation of catanionic mixtures of ctac/sds induced by ratio: a coarse-grained molecular dynamic simulation study. RSC Advances,  2016, 6, 13442-13449.
[http://dx.doi.org/10.1039/C5RA26051E] 
[230] 
Marrink, S.J.; Mark, A.E. Molecular dynamics simulation of the formation, structure, and dynamics of small phospholipid vesicles. J. Am. Chem. Soc.,  2003, 125(49), 15233-15242.
[http://dx.doi.org/10.1021/ja0352092] [PMID: 14653758] 
[231] 
Chng, C-P. Effect of simulation temperature on phospholipid bilayer-vesicle transition studied by coarse-grained molecular dynamics simulations. Soft Matter,  2013, 9, 7294-7301.
[http://dx.doi.org/10.1039/c3sm51038g] 
[232] 
Sun, X-L.; Pei, S.; Wang, J-F.; Wang, P.; Liu, Z-B.; Zhang, J. Coarse-grained molecular dynamics simulation study on spherical and tube-like vesicles formed by amphiphilic copolymers. J. Polym. Sci., B, Polym. Phys.,  2017, 55, 1220-1226.
[http://dx.doi.org/10.1002/polb.24376] 
[233] 
de Vries, A.H.; Mark, A.E.; Marrink, S.J. Molecular dynamics simulation of the spontaneous formation of a small DPPC vesicle in water in atomistic detail. J. Am. Chem. Soc.,  2004, 126(14), 4488-4489.
[http://dx.doi.org/10.1021/ja0398417] [PMID: 15070345] 
[234] 
Parchekani Choozaki, J.; Taghdir, M. Investigation the effect of cholesterol on the formation and stability of the liposomes using coarse-grained molecular dynamics simulations. Modares J. Biotech.,  2019, 10, 241-246.
[235] 
Koshiyama, K.; Wada, S. Collapse of a lipid-coated nanobubble and subsequent liposome formation. Sci. Rep.,  2016, 6, 28164.
[http://dx.doi.org/10.1038/srep28164] [PMID: 27306704] 
[236] 
Knecht, V.; Marrink, S-J. Molecular dynamics simulations of lipid vesicle fusion in atomic detail. Biophys. J.,  2007, 92(12), 4254-4261.
[http://dx.doi.org/10.1529/biophysj.106.103572] [PMID: 17384060] 
[237] 
Marrink, S.J.; Mark, A.E. The mechanism of vesicle fusion as revealed by molecular dynamics simulations. J. Am. Chem. Soc.,  2003, 125(37), 11144-11145.
[http://dx.doi.org/10.1021/ja036138+] [PMID: 16220905] 
[238] 
Pannuzzo, M.; De Jong, D.H.; Raudino, A.; Marrink, S.J. Simulation of polyethylene glycol and calcium-mediated membrane fusion. J. Chem. Phys.,  2014, 140(12)124905
[http://dx.doi.org/10.1063/1.4869176] [PMID: 24697479] 
[239] 
Venable, R.M.; Ingólfsson, H.I.; Lerner, M.G.; Perrin, B.S., Jr; Camley, B.A.; Marrink, S.J.; Brown, F.L.H.; Pastor, R.W. Lipid and peptide diffusion in bilayers: the saffman-delbrück model and periodic boundary conditions. J. Phys. Chem. B,  2017, 121(15), 3443-3457.
[http://dx.doi.org/10.1021/acs.jpcb.6b09111] [PMID: 27966982] 
[240] 
Baoukina, S.; Tieleman, D.P. Direct simulation of protein-mediated vesicle fusion: lung surfactant protein B. Biophys. J.,  2010, 99(7), 2134-2142.
[http://dx.doi.org/10.1016/j.bpj.2010.07.049] [PMID: 20923647] 
[241] 
Li, Y.; Li, X.; Li, Z.; Gao, H. Surface-structure-regulated penetration of nanoparticles across a cell membrane. Nanoscale,  2012, 4(12), 3768-3775.
[http://dx.doi.org/10.1039/c2nr30379e] [PMID: 22609866] 
[242] 
Chen, L.; Wu, Z.; Wu, X.; Liao, Y.; Dai, X.; Shi, X. The application of coarse-grained molecular dynamics to the evaluation of liposome physical stability. AAPS PharmSciTech,  2020, 21(5), 138.
[http://dx.doi.org/10.1208/s12249-020-01680-6] [PMID: 32419093] 
[243] 
Tamai, H.; Okutsu, N.; Tokuyama, Y.; Shimizu, E.; Miyagi, S.; Shulga, S.; Danilov, V.I.; Kurita, N. A coarse grained molecular dynamics study on the structure and stability of small-sized liposomes. Mol. Simul.,  2016, 42, 122-130.
[http://dx.doi.org/10.1080/08927022.2015.1020487] 
[244] 
Risselada, H.J.; Marrink, S.J.; Müller, M. Curvature-dependent elastic properties of liquid-ordered domains result in inverted domain sorting on uniaxially compressed vesicles. Phys. Rev. Lett.,  2011, 106(14)148102
[http://dx.doi.org/10.1103/PhysRevLett.106.148102] [PMID: 21561224] 
[245] 
Risselada, H.J.; Marrink, S.J. Curvature effects on lipid packing and dynamics in liposomes revealed by coarse grained molecular dynamics simulations. Phys. Chem. Chem. Phys.,  2009, 11(12), 2056-2067.
[http://dx.doi.org/10.1039/b818782g] [PMID: 19280016] 
[246] 
Semple, S.C.; Akinc, A.; Chen, J.; Sandhu, A.P.; Mui, B.L.; Cho, C.K.; Sah, D.W.Y.; Stebbing, D.; Crosley, E.J.; Yaworski, E.; Hafez, I.M.; Dorkin, J.R.; Qin, J.; Lam, K.; Rajeev, K.G.; Wong, K.F.; Jeffs, L.B.; Nechev, L.; Eisenhardt, M.L.; Jayaraman, M.; Kazem, M.; Maier, M.A.; Srinivasulu, M.; Weinstein, M.J.; Chen, Q.; Alvarez, R.; Barros, S.A.; De, S.; Klimuk, S.K.; Borland, T.; Kosovrasti, V.; Cantley, W.L.; Tam, Y.K.; Manoharan, M.; Ciufolini, M.A.; Tracy, M.A.; de Fougerolles, A.; MacLachlan, I.; Cullis, P.R.; Madden, T.D.; Hope, M.J. Rational design of cationic lipids for siRNA delivery. Nat. Biotechnol.,  2010, 28(2), 172-176.
[http://dx.doi.org/10.1038/nbt.1602] [PMID: 20081866] 
[247] 
Jämbeck, J.P.M.; Eriksson, E.S.E.; Laaksonen, A.; Lyubartsev, A.P.; Eriksson, L.A. Molecular dynamics studies of liposomes as carriers for photosensitizing drugs: development, validation, and simulations with a coarse-grained model. J. Chem. Theory Comput.,  2014, 10(1), 5-13.
[http://dx.doi.org/10.1021/ct400466m] [PMID: 26579887] 
[248] 
Genheden, S.; Eriksson, L.A. Estimation of liposome penetration barriers of drug molecules with all-atom and coarse-grained models. J. Chem. Theory Comput.,  2016, 12(9), 4651-4661.
[http://dx.doi.org/10.1021/acs.jctc.6b00557] [PMID: 27541708] 
[249] 
Pickholz, M.; Giupponi, G. Coarse grained simulations of local anesthetics encapsulated into a liposome. J. Phys. Chem. B,  2010, 114(20), 7009-7015.
[http://dx.doi.org/10.1021/jp909148n] [PMID: 20429599] 
[250] 
Genheden, S. Solvation free energies and partition coefficients with the coarse-grained and hybrid all-atom/coarse-grained MARTINI models. J. Comput. Aided Mol. Des.,  2017, 31(10), 867-876.
[http://dx.doi.org/10.1007/s10822-017-0059-9] [PMID: 28875361] 
[251] 
Leung, A.K.K.; Hafez, I.M.; Baoukina, S.; Belliveau, N.M.; Zhigaltsev, I.V.; Afshinmanesh, E.; Tieleman, D.P.; Hansen, C.L.; Hope, M.J.; Cullis, P.R. Lipid nanoparticles containing sirna synthesized by microfluidic mixing exhibit an electron-dense nanostructured core. J Phys. Chem. C. Nanomater. Interfaces,  2012, 116(34), 18440-18450.
[http://dx.doi.org/10.1021/jp303267y] [PMID: 22962627] 
[252] 
Menichetti, R.; Kanekal, K.H.; Kremer, K.; Bereau, T. In silico screening of drug-membrane thermodynamics reveals linear relations between bulk partitioning and the potential of mean force. J. Chem. Phys.,  2017, 147(12)125101
[http://dx.doi.org/10.1063/1.4987012] [PMID: 28964031] 
[253] 
Menichetti, R.; Bereau, T. Revisiting the meyer-overton rule for drug-membrane permeabilities. Mol. Phys.,  2019, 117, 2900-2909.
[http://dx.doi.org/10.1080/00268976.2019.1601787] 
[254] 
Menichetti, R.; Kanekal, K.H.; Bereau, T. Drug-membrane permeability across chemical space. ACS Cent. Sci.,  2019, 5(2), 290-298.
[http://dx.doi.org/10.1021/acscentsci.8b00718] [PMID: 30834317] 
[255] 
Aydin, F.; Ludford, P.; Dutt, M. Phase segregation in bio-inspired multi-component vesicles encompassing double tail phospholipid species. Soft Matter,  2014, 10(32), 6096-6108.
[http://dx.doi.org/10.1039/C4SM00998C] [PMID: 25008809] 
[256] 
Li, X.; Tang, Y-H.; Liang, H.; Karniadakis, G.E. Large-scale dissipative particle dynamics simulations of self-assembled amphiphilic systems. Chem. Commun. (Camb.),  2014, 50(61), 8306-8308.
[http://dx.doi.org/10.1039/C4CC03096F] [PMID: 24938634] 
[257] 
Wang, M.; Pei, S.; Fang, T.; Yan, Y.; Xu, J.; Zhang, J. Dissipative particle dynamics simulation on vesicles self-assembly controlled by terminal groups. J. Phys. Chem. B,  2018, 122(46), 10607-10614.
[http://dx.doi.org/10.1021/acs.jpcb.8b07567] [PMID: 30380871] 
[258] 
Jia, L.; Wang, R.; Fan, Y. Encapsulation and release of drug nanoparticles in functional polymeric vesicles. Soft Matter,  2020, 16(12), 3088-3095.
[http://dx.doi.org/10.1039/D0SM00069H] [PMID: 32149316] 
[259] 
Spaeth, J.R.; Kevrekidis, I.G.; Panagiotopoulos, A.Z. Dissipative particle dynamics simulations of polymer-protected nanoparticle self-assembly. J. Chem. Phys.,  2011, 135(18)184903
[http://dx.doi.org/10.1063/1.3653379] [PMID: 22088077] 
[260] 
Noguchi, H. Dynamical modes of deformed red blood cells and lipid vesicles in flows. Prog. Theor. Phys.,  2010, 184, 364-368.
[http://dx.doi.org/10.1143/PTPS.184.364] 
[261] 
Noguchi, H.; Takasu, M. Self-assembly of amphiphiles into vesicles: a Brownian dynamics simulation. Phys. Rev. E Stat. Nonlin. Soft Matter Phys.,  2001, 64(4 Pt 1)041913
[http://dx.doi.org/10.1103/PhysRevE.64.041913] [PMID: 11690058] 
[262] 
Noguchi, H.; Takasu, M. Fusion pathways of vesicles: a brownian dynamics simulation. J. Chem. Phys.,  2001, 115, 9547-9551.
[http://dx.doi.org/10.1063/1.1414314] 
[263] 
Le, T.; Epa, V.C.; Burden, F.R.; Winkler, D.A. Quantitative structure-property relationship modeling of diverse materials properties. Chem. Rev.,  2012, 112(5), 2889-2919.
[http://dx.doi.org/10.1021/cr200066h] [PMID: 22251444] 
[264] 
Le, T.C.; Tran, N. Using machine learning to predict the self-assembled nanostructures of monoolein and phytantriol as a function of temperature and fatty acid additives for effective lipid-based delivery systems. ACS Appl. Nano Mater.,  2019, 2, 1637-1647.
[http://dx.doi.org/10.1021/acsanm.9b00075] 
[265] 
Tran, N.; Mulet, X.; Hawley, A.M.; Fong, C.; Zhai, J.; Le, T.C.; Ratcliffe, J.; Drummond, C.J. Manipulating the ordered nanostructure of self-assembled monoolein and phytantriol nanoparticles with unsaturated fatty acids. Langmuir,  2018, 34(8), 2764-2773.
[http://dx.doi.org/10.1021/acs.langmuir.7b03541] [PMID: 29381863] 
[266] 
Tran, N.; Hawley, A.M.; Zhai, J.; Muir, B.W.; Fong, C.; Drummond, C.J.; Mulet, X. High-Throughput Screening of saturated fatty acid influence on nanostructure of lyotropic liquid crystalline lipid nanoparticles. Langmuir,  2016, 32(18), 4509-4520.
[http://dx.doi.org/10.1021/acs.langmuir.5b03769] [PMID: 27023315] 
[267] 
Speck-Planche, A.; Kleandrova, V.V.; Luan, F.; Cordeiro, M.N.; Computational Modeling, M.N. Computational modeling in nanomedicine: prediction of multiple antibacterial profiles of nanoparticles using a quantitative structure-activity relationship perturbation model. Nanomedicine (Lond.),  2015, 10(2), 193-204.
[http://dx.doi.org/10.2217/nnm.14.96] [PMID: 25600965] 
[268] 
Concu, R.; Kleandrova, V.V.; Speck-Planche, A.; Cordeiro, M.N.D.S. Probing the toxicity of nanoparticles: a unified in silico machine learning model based on perturbation theory. Nanotoxicology,  2017, 11(7), 891-906.
[http://dx.doi.org/10.1080/17435390.2017.1379567] [PMID: 28937298] 
[269] 
Luan, F.; Kleandrova, V.V.; González-Díaz, H.; Ruso, J.M.; Melo, A.; Speck-Planche, A.; Cordeiro, M.N.D.S. Computer-aided nanotoxicology: assessing cytotoxicity of nanoparticles under diverse experimental conditions by using a novel QSTR-perturbation approach. Nanoscale,  2014, 6(18), 10623-10630.
[http://dx.doi.org/10.1039/C4NR01285B] [PMID: 25083742] 
[270] 
González-Díaz, H.; Arrasate, S.; Gómez-SanJuan, A.; Sotomayor, N.; Lete, E.; Besada-Porto, L.; Ruso, J.M. General theory for multiple input-output perturbations in complex molecular systems. 1. Linear QSPR electronegativity models in physical, organic, and medicinal chemistry. Curr. Top. Med. Chem.,  2013, 13(14), 1713-1741.
[http://dx.doi.org/10.2174/1568026611313140011] [PMID: 23889050] 
[271] 
Santana, R.; Zuluaga, R.; Gañán, P.; Arrasate, S.; Onieva, E.; González-Díaz, H. Designing nanoparticle release systems for drug-vitamin cancer co-therapy with multiplicative perturbation-theory machine learning (PTML) models. Nanoscale,  2019, 11(45), 21811-21823.
[http://dx.doi.org/10.1039/C9NR05070A] [PMID: 31691701] 
[272] 
Santana, R.; Zuluaga, R.; Gañán, P.; Arrasate, S.; Onieva, E.; González-Díaz, H. Predicting coated-nanoparticle drug release systems with perturbation-theory machine learning (PTML) models. Nanoscale,  2020, 12(25), 13471-13483.
[http://dx.doi.org/10.1039/D0NR01849J] [PMID: 32613998] 
[273] 
Yamankurt, G.; Berns, E.J.; Xue, A.; Lee, A.; Bagheri, N.; Mrksich, M.; Mirkin, C.A. Exploration of the nanomedicine-design space with high-throughput screening and machine learning. Nat. Biomed. Eng.,  2019, 3(4), 318-327.
[http://dx.doi.org/10.1038/s41551-019-0351-1] [PMID: 30952978] 
[274] 
Jones, D.E.; Ghandehari, H.; Facelli, J.C. A review of the applications of data mining and machine learning for the prediction of biomedical properties of nanoparticles. Comput. Methods Programs Biomed.,  2016, 132, 93-103.
[http://dx.doi.org/10.1016/j.cmpb.2016.04.025] [PMID: 27282231] 
[275] 
Epa, V.C.; Burden, F.R.; Tassa, C.; Weissleder, R.; Shaw, S.; Winkler, D.A. Modeling biological activities of nanoparticles. Nano Lett.,  2012, 12(11), 5808-5812.
[http://dx.doi.org/10.1021/nl303144k] [PMID: 23039907] 
[276] 
Metwally, A.A.; Hathout, R.M. Computer-assisted drug formulation design: novel approach in drug delivery. Mol. Pharm.,  2015, 12(8), 2800-2810.
[http://dx.doi.org/10.1021/mp500740d] [PMID: 26107396] 
[277] 
Hathout, R.M.; Metwally, A.A. Towards better modelling of drug-loading in solid lipid nanoparticles: Molecular dynamics, docking experiments and Gaussian Processes machine learning. Eur. J. Pharm. Biopharm.,  2016, 108, 262-268.
[http://dx.doi.org/10.1016/j.ejpb.2016.07.019] [PMID: 27449631] 
[278] 
Metwally, A.A.; Hathout, R.M. Replacing microemulsion formulations experimental solubility studies with in-silico methods comprising molecular dynamics and docking experiments. Chem. Eng. Res. Des.,  2015, 104, 453-456.
[http://dx.doi.org/10.1016/j.cherd.2015.09.003] 
[279] 
Uttarwar, R.G.; Potoff, J.; Huang, Y. Study on interfacial interaction between polymer and nanoparticle in a nanocoating matrix: a martini coarse-graining method. Ind. Eng. Chem. Res.,  2013, 52, 73-82.
[http://dx.doi.org/10.1021/ie301228f] 
[280] 
Saunders, L.; Perrin, J.; Gammack, D. Ultrasonic irradiation of some phospholipid sols. J. Pharm. Pharmacol.,  1962, 14, 567-572.
[http://dx.doi.org/10.1111/j.2042-7158.1962.tb11141.x] [PMID: 14497533] 
[281] 
Hargreaves, W.R.; Deamer, D.W. Liposomes from ionic, single-chain amphiphiles. Biochemistry,  1978, 17(18), 3759-3768.
[http://dx.doi.org/10.1021/bi00611a014] [PMID: 698196] 
[282] 
Parente, R.A.; Lentz, B.R. Phase behavior of large unilamellar vesicles composed of synthetic phospholipids. Biochemistry,  1984, 23(11), 2353-2362.
[http://dx.doi.org/10.1021/bi00306a005] [PMID: 6477871] 
[283] 
Song, H.; Geng, H.; Ruan, J.; Wang, K.; Bao, C.; Wang, J.; Peng, X.; Zhang, X.; Cui, D. Development of Polysorbate 80/Phospholipid mixed micellar formation for docetaxel and assessment of its in vivo distribution in animal models. Nanoscale Res. Lett.,  2011, 6(1), 354.
[http://dx.doi.org/10.1186/1556-276X-6-354] [PMID: 21711889] 
[284] 
Stano, P.; Bufali, S.; Pisano, C.; Bucci, F.; Barbarino, M.; Santaniello, M.; Carminati, P.; Luisi, P.L. Novel camptothecin analogue (gimatecan)-containing liposomes prepared by the ethanol injection method. J. Liposome Res.,  2004, 14(1-2), 87-109.
[http://dx.doi.org/10.1081/LPR-120039794] [PMID: 15461935] 
[285] 
Ohsawa, T.; Miura, H.; Harada, K. Improvement of encapsulation efficiency of water-soluble drugs in liposomes formed by the freeze-thawing method. Chem. Pharm. Bull. (Tokyo),  1985, 33(9), 3945-3952.
[http://dx.doi.org/10.1248/cpb.33.3945] [PMID: 4092294] 
[286] 
Liu, L.; Yonetani, T. Preparation and characterization of liposome-encapsulated haemoglobin by a freeze-thaw method. J. Microencapsul.,  1994, 11(4), 409-421.
[http://dx.doi.org/10.3109/02652049409034258] [PMID: 7931940] 
[287] 
Schieren, H.; Rudolph, S.; Finkelstein, M.; Coleman, P.; Weissmann, G. Comparison of large unilamellar vesicles prepared by a petroleum ether vaporization method with multilamellar vesicles: ESR, diffusion and entrapment analyses. Biochim. Biophys. Acta,  1978, 542(1), 137-153.
[http://dx.doi.org/10.1016/0304-4165(78)90240-4] [PMID: 208648] 
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DOI https://dx.doi.org/10.2174/1568026620666201126162945	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294
Current Topics in Medicinal Chemistry

Computational and Experimental Approaches to Investigate Lipid Nanoparticles as Drug and Gene Delivery Systems

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