Generic placeholder image

Pharmaceutical Nanotechnology

Editor-in-Chief

ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Review Article

Challenges and Therapeutic Approaches for the Protein Delivery System: A Review

Author(s): Devashish Jena, Nimisha Srivastava*, Iti Chauhan and Madhu Verma

Volume 12, Issue 5, 2024

Published on: 08 January, 2024

Page: [391 - 411] Pages: 21

DOI: 10.2174/0122117385265979231115074255

Price: $65

Abstract

The protein delivery system is one of the innovative or novel drug delivery systems in the present era. Proteins play an indispensable role in our body and are mainly found in every part, like tissue and cells of our body. It also controls various functions, such as maintaining our tissue, transportation, muscle recovery, enzyme production and acting as an energy source for our body. Protein therapeutics have big future perspectives, and their use in the treatment of a wide range of serious diseases has transformed the delivery system in the pharmaceutical and biotechnology industries.

The chief advantage of protein delivery is that it can be delivered directly to the systemic circulation. So far, parenteral routes, such as intravenous, intramuscular, and subcutaneous, are the most often used method of administering protein drugs. Alternative routes like buccal, oral, pulmonary, transdermal, nasal, and ocular routes have also shown a remarkable success rate.

However, as with all other types of delivery, here, several challenges are posed due to the presence of various barriers, such as the enzymatic barrier, intestinal epithelial barrier, capillary endothelial barrier, and blood-brain barrier. There are several approaches that have been explored to overcome these barriers, such as chemical modification, enzymatic inhibitors, penetration enhancers, and mucoadhesive polymers. This review article discusses the protein, its functions, routes of administration, challenges, and strategies to achieve ultimate formulation goals. Recent advancements like the protein Pegylation method and Depofoam technology are another highlight of the article.

Graphical Abstract

[1]
Branden CI, Tooze J. Introduction to protein structure. Garland Science 2012.
[http://dx.doi.org/10.1201/9781136969898]
[2]
Lesk A. Introduction to protein science: architecture, function, and genomics. Oxford university press 2010.
[3]
Ferrer-Miralles N, Saccardo P, Corchero JL, Xu Z, García-Fruitós E. General introduction: recombinant protein production and purification of insoluble proteins. Insoluble Proteins 2015; pp. 1-24.
[4]
Nussinov R. Introduction to protein ensembles and allostery. Chem Rev 2016; 116(11): 6263-6.
[http://dx.doi.org/10.1021/acs.chemrev.6b00283] [PMID: 27268255]
[5]
Janson JC. Ed Protein purification: principles, high-resolution methods, and applications. John Wiley & Sons 2012.
[6]
Carter PJ. Introduction to current and future protein therapeutics: A protein engineering perspective. Exp Cell Res 2011; 317(9): 1261-9.
[http://dx.doi.org/10.1016/j.yexcr.2011.02.013] [PMID: 21371474]
[7]
Lesk AM. Introduction to protein architecture: the structural biology of proteins. Oxford: Oxford university press 2001.
[8]
Lee WT. An interactive introduction to protein structure. Biochem Mol Biol Educ 2004; 32(3): 170-2.
[http://dx.doi.org/10.1002/bmb.2004.494032030354] [PMID: 21706717]
[9]
Sachs JN, Engelman DM. Introduction to the membrane protein reviews: the interplay of structure, dynamics, and environment in membrane protein function. Annu Rev Biochem 2006; 75(1): 707-12.
[http://dx.doi.org/10.1146/annurev.biochem.75.110105.142336] [PMID: 16756508]
[10]
Carton JM, Strohl WR. Protein therapeutics (introduction to biopharmaceuticals). In: Introduction to Biological and Small Molecule Drug Research and Development. Elsevier 2013; pp. 127-59.
[11]
Bajaj M, Blundell T. Evolution and the tertiary structure of proteins. Annu Rev Biophys Bioeng 1984; 13(1): 453-92.
[http://dx.doi.org/10.1146/annurev.bb.13.060184.002321] [PMID: 6378074]
[12]
Benjamin DC, Berzofsky JA, East IJ, et al. The antigenic structure of proteins: a reappraisal. Annu Rev Immunol 1984; 2(1): 67-101.
[http://dx.doi.org/10.1146/annurev.iy.02.040184.000435] [PMID: 6085753]
[13]
Arrondo JLR, Muga A, Castresana J, Goñi FM. Quantitative studies of the structure of proteins in solution by fourier-transform infrared spectroscopy. Prog Biophys Mol Biol 1993; 59(1): 23-56.
[http://dx.doi.org/10.1016/0079-6107(93)90006-6] [PMID: 8419985]
[14]
Chothia C, Levitt M, Richardson D. Structure of proteins: packing of alpha-helices and pleated sheets. Proc Natl Acad Sci USA 1977; 74(10): 4130-4.
[http://dx.doi.org/10.1073/pnas.74.10.4130] [PMID: 270659]
[15]
Johnson WC Jr. Secondary structure of proteins through circular dichroism spectroscopy. Annu Rev Biophys Biophys Chem 1988; 17(1): 145-66.
[http://dx.doi.org/10.1146/annurev.bb.17.060188.001045] [PMID: 3293583]
[16]
Unger R, Harel D, Wherland S, Sussman JL. A 3D building blocks approach to analyzing and predicting structure of proteins. Proteins 1989; 5(4): 355-73.
[http://dx.doi.org/10.1002/prot.340050410] [PMID: 2798411]
[17]
Paulick MG, Bertozzi CR. The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins. Biochemistry 2008; 47(27): 6991-7000.
[http://dx.doi.org/10.1021/bi8006324] [PMID: 18557633]
[18]
Isralewitz B, Gao M, Schulten K. Steered molecular dynamics and mechanical functions of proteins. Curr Opin Struct Biol 2001; 11(2): 224-30.
[http://dx.doi.org/10.1016/S0959-440X(00)00194-9] [PMID: 11297932]
[19]
Sarkar SN, Sen GC. Novel functions of proteins encoded by viral stress-inducible genes. Pharmacol Ther 2004; 103(3): 245-59.
[http://dx.doi.org/10.1016/j.pharmthera.2004.07.007] [PMID: 15464592]
[20]
Hinman MN, Lou H. Diverse molecular functions of Hu proteins. Cell Mol Life Sci 2008; 65(20): 3168-81.
[http://dx.doi.org/10.1007/s00018-008-8252-6] [PMID: 18581050]
[21]
Damodaran S. Food proteins and their applications. CRC Press 2017.
[http://dx.doi.org/10.1201/9780203755617]
[22]
Saba Saeed , Mavra Irfan, Saima Naz, Momil Liaquat, Shafaq Jahan , Sana Hayat . Routes and barriers associated with protein and peptide drug delivery system. J Pak Med Assoc 2021; 71(8): 2032-9.
[http://dx.doi.org/10.47391/JPMA.759] [PMID: 34418025]
[23]
Lyu Y, Azevedo HS. Supramolecular Hydrogels for Protein Delivery in Tissue Engineering. Molecules 2021; 26(4): 873.
[http://dx.doi.org/10.3390/molecules26040873] [PMID: 33562215]
[24]
Zhu Q, Chen Z, Paul PK, Lu Y, Wu W, Qi J. Oral delivery of proteins and peptides: Challenges, status quo and future perspectives. Acta Pharm Sin B 2021; 11(8): 2416-48.
[http://dx.doi.org/10.1016/j.apsb.2021.04.001] [PMID: 34522593]
[25]
Bajracharya R, Song JG, Back SY, Han HK. Recent advancements in non-invasive formulations for protein drug delivery. Comput Struct Biotechnol J 2019; 17: 1290-308.
[http://dx.doi.org/10.1016/j.csbj.2019.09.004] [PMID: 31921395]
[26]
Savale SK. Protein and peptide drug delivery system. World J Pharm Sci 2016; 5(4): 1-9.
[27]
Bruno BJ, Miller GD, Lim CS. Basics and recent advances in peptide and protein drug delivery. Ther Deliv 2013; 4(11): 1443-67.
[http://dx.doi.org/10.4155/tde.13.104] [PMID: 24228993]
[28]
Elzoghby AO, Samy WM, Elgindy NA. Protein-based nanocarriers as promising drug and gene delivery systems. J Control Release 2012; 161(1): 38-49.
[http://dx.doi.org/10.1016/j.jconrel.2012.04.036] [PMID: 22564368]
[29]
Anselmo AC, Mitragotri S. An overview of clinical and commercial impact of drug delivery systems. J Control Release 2014; 190: 15-28.
[http://dx.doi.org/10.1016/j.jconrel.2014.03.053] [PMID: 24747160]
[30]
Gupta H, Sharma A. Recent trends in protein and peptide drug delivery systems. Asian J Pharm 2014; 3.
[31]
Shaji J, Patole V. Protein and peptide drug delivery: Oral approaches. Indian J Pharm Sci 2008; 70(3): 269-77.
[http://dx.doi.org/10.4103/0250-474X.42967] [PMID: 20046732]
[32]
Venkata Ramana Rao S, Shao J. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs. Int J Pharm 2008; 362(1-2): 2-9.
[http://dx.doi.org/10.1016/j.ijpharm.2008.05.018] [PMID: 18650038]
[33]
Kumar Malik D, Baboota S, Ahuja A, Hasan S, Ali J. Recent advances in protein and peptide drug delivery systems. Curr Drug Deliv 2007; 4(2): 141-51.
[http://dx.doi.org/10.2174/156720107780362339] [PMID: 17456033]
[34]
Narhi LO, Schmit J, Bechtold-Peters K, Sharma D. Classification of protein aggregates. J Pharm Sci 2012; 101(2): 493-8.
[http://dx.doi.org/10.1002/jps.22790] [PMID: 21989781]
[35]
Tolstoguzov VB. Functional properties of protein–polysaccharide mixtures. In: Functional properties of food macromolecules. 1986; pp. 385-415.
[36]
Anson ML. Protein denaturation and the properties of protein groupsAdvances in protein chemistry. Academic Press 1945; Vol. 2: pp. 361-86.
[37]
Björk I, Petersson BA, Sjöquist J. Some physiochemical properties of protein A from Staphylococcus aureus. Eur J Biochem 1972; 29(3): 579-84.
[http://dx.doi.org/10.1111/j.1432-1033.1972.tb02024.x] [PMID: 5083510]
[38]
Wihodo M, Moraru CI. Physical and chemical methods used to enhance the structure and mechanical properties of protein films: A review. J Food Eng 2013; 114(3): 292-302.
[http://dx.doi.org/10.1016/j.jfoodeng.2012.08.021]
[39]
Foegeding EA, Luck PJ, Davis JP. Factors determining the physical properties of protein foams. Food Hydrocoll 2006; 20(2-3): 284-92.
[http://dx.doi.org/10.1016/j.foodhyd.2005.03.014]
[40]
Chau CF, Cheung PCK, Wong YS. Functional properties of protein concentrates from three Chinese indigenous legume seeds. J Agric Food Chem 1997; 45(7): 2500-3.
[http://dx.doi.org/10.1021/jf970047c]
[41]
Ogunwolu SO, Henshaw FO, Mock HP, Santros A, Awonorin SO. Functional properties of protein concentrates and isolates produced from cashew (Anacardium occidentale L.) nut. Food Chem 2009; 115(3): 852-8.
[http://dx.doi.org/10.1016/j.foodchem.2009.01.011]
[42]
Woodley JF. Enzymatic barriers for GI peptide and protein delivery. Crit Rev Ther Drug Carrier Syst 1994; 11(2-3): 61-95.
[PMID: 7600588]
[43]
Li N, Li XR, Zhou YX, et al. The use of polyion complex micelles to enhance the oral delivery of salmon calcitonin and transport mechanism across the intestinal epithelial barrier. Biomaterials 2012; 33(34): 8881-92.
[http://dx.doi.org/10.1016/j.biomaterials.2012.08.047] [PMID: 22975427]
[44]
Rosenthal R, Günzel D, Finger C, et al. The effect of chitosan on transcellular and paracellular mechanisms in the intestinal epithelial barrier. Biomaterials 2012; 33(9): 2791-800.
[http://dx.doi.org/10.1016/j.biomaterials.2011.12.034] [PMID: 22230222]
[45]
Yu Q, Yang Q. Diversity of tight junctions (TJs) between gastrointestinal epithelial cells and their function in maintaining the mucosal barrier. Cell Biol Int 2009; 33(1): 78-82.
[http://dx.doi.org/10.1016/j.cellbi.2008.09.007] [PMID: 18938254]
[46]
Rawat A, Burgess DJ. Parenteral delivery of peptides and proteins. Biodrug Delivery Systems 2016; 66-84.
[47]
Lawther BK, Kumar S, Krovvidi H. Blood–brain barrier. Contin Educ Anaesth Crit Care Pain 2011; 11(4): 128-32.
[http://dx.doi.org/10.1093/bjaceaccp/mkr018]
[48]
Chen G, Kang W, Li W, Chen S, Gao Y. Oral delivery of protein and peptide drugs: from non-specific formulation approaches to intestinal cell targeting strategies. Theranostics 2022; 12(3): 1419-39.
[http://dx.doi.org/10.7150/thno.61747] [PMID: 35154498]
[49]
Patel A, Cholkar K, Mitra AK. Recent developments in protein and peptide parenteral delivery approaches. Ther Deliv 2014; 5(3): 337-65.
[http://dx.doi.org/10.4155/tde.14.5] [PMID: 24592957]
[50]
Jain D, Mahammad SS, Singh PP, Kodipyaka R. A review on parenteral delivery of peptides and proteins. Drug Dev Ind Pharm 2019; 45(9): 1403-20.
[http://dx.doi.org/10.1080/03639045.2019.1628770] [PMID: 31215293]
[51]
Caon T, Jin L, Simões CMO, Norton RS, Nicolazzo JA. Enhancing the buccal mucosal delivery of peptide and protein therapeutics. Pharm Res 2015; 32(1): 1-21.
[http://dx.doi.org/10.1007/s11095-014-1485-1] [PMID: 25168518]
[52]
Senel S, Kremer M, Katalin N, Squier C. Delivery of bioactive peptides and proteins across oral (buccal) mucosa. Curr Pharm Biotechnol 2001; 2(2): 175-86.
[http://dx.doi.org/10.2174/1389201013378734] [PMID: 11480421]
[53]
Jitendra PK, Sharma PK, Bansal S, Banik A. Noninvasive routes of proteins and peptides drug delivery. Indian J Pharm Sci 2011; 73(4): 367-75.
[PMID: 22707818]
[54]
Morishita M, Peppas NA. Is the oral route possible for peptide and protein drug delivery? Drug Discov Today 2006; 11(19-20): 905-10.
[http://dx.doi.org/10.1016/j.drudis.2006.08.005] [PMID: 16997140]
[55]
Verma S, Goand UK, Husain A, Katekar RA, Garg R, Gayen JR. Challenges of peptide and protein drug delivery by oral route: Current strategies to improve the bioavailability. Drug Dev Res 2021; 82(7): 927-44.
[http://dx.doi.org/10.1002/ddr.21832] [PMID: 33988872]
[56]
Choonara BF, Choonara YE, Kumar P, Bijukumar D, du Toit LC, Pillay V. A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules. Biotechnol Adv 2014; 32(7): 1269-82.
[http://dx.doi.org/10.1016/j.biotechadv.2014.07.006] [PMID: 25099657]
[57]
Hussain A, Arnold JJ, Khan MA, Ahsan F. Absorption enhancers in pulmonary protein delivery. J Control Release 2004; 94(1): 15-24.
[http://dx.doi.org/10.1016/j.jconrel.2003.10.001] [PMID: 14684268]
[58]
Smith PL. Peptide delivery via the pulmonary route: a valid approach for local and systemic delivery. J Control Release 1997; 46(1-2): 99-106.
[http://dx.doi.org/10.1016/S0168-3659(96)01579-9]
[59]
Benson HAE, Namjoshi S. Proteins and peptides: strategies for delivery to and across the skin. J Pharm Sci 2008; 97(9): 3591-610.
[http://dx.doi.org/10.1002/jps.21277] [PMID: 18200531]
[60]
Dychter SS, Gold DA, Haller MF. Subcutaneous drug delivery: a route to increased safety, patient satisfaction, and reduced costs. J Infus Nurs 2012; 35(3): 154-60.
[http://dx.doi.org/10.1097/NAN.0b013e31824d2271] [PMID: 22498485]
[61]
Kalluri H, Banga AK. Transdermal delivery of proteins. AAPS PharmSciTech 2011; 12(1): 431-41.
[http://dx.doi.org/10.1208/s12249-011-9601-6] [PMID: 21369712]
[62]
Jadhav K, Gambhire M, Shaikh I, Kadam V, Pisal S. Nasal drug delivery system-factors affecting and applications. Curr Drug Ther 2007; 2(1): 27-38.
[http://dx.doi.org/10.2174/157488507779422374]
[63]
Ingemann ME, Frokjaer SV, Hovgaard LA, Brøndsted HE. Peptide and protein drug delivery systems for non-parenteral routes of administration. In: Pharmaceutical formulation development of peptides and proteins. 2000; p. 189.
[64]
Ozer AY. Alternative applications for drug delivery: nasal and pulmonary routes InNanomaterials and nanosystems for biomedical applications. Dordrecht: Springer 2007; pp. 99-112.
[65]
Rahisuddin SP, Garg G, Salim M. Review on nasal drug delivery system with recent advancement. Int J Pharm Pharm Sci 2011; 3(2): 1-5.
[66]
Vyas SP, Paliwal R, Paliwal SR. Ocular delivery of peptides and proteins. Peptide and protein delivery 2011; 87-103.
[http://dx.doi.org/10.1016/B978-0-12-384935-9.10005-7]
[67]
Mandal A, Pal D, Agrahari V, Trinh HM, Joseph M, Mitra AK. Ocular delivery of proteins and peptides: Challenges and novel formulation approaches. Adv Drug Deliv Rev 2018; 126: 67-95.
[http://dx.doi.org/10.1016/j.addr.2018.01.008] [PMID: 29339145]
[68]
Banks SR, Enck K, Wright M, Opara EC, Welker ME. Chemical modification of alginate for controlled oral drug delivery. J Agric Food Chem 2019; 67(37): 10481-8.
[http://dx.doi.org/10.1021/acs.jafc.9b01911] [PMID: 31433940]
[69]
Chalker JM, Bernardes GJL, Lin YA, Davis BG. Chemical modification of proteins at cysteine: opportunities in chemistry and biology. Chem Asian J 2009; 4(5): 630-40.
[http://dx.doi.org/10.1002/asia.200800427] [PMID: 19235822]
[70]
Bernkop-Schnürch A. The use of inhibitory agents to overcome the enzymatic barrier to perorally administered therapeutic peptides and proteins. J Control Release 1998; 52(1-2): 1-16.
[http://dx.doi.org/10.1016/S0168-3659(97)00204-6] [PMID: 9685931]
[71]
Sinha VR, Trehan A. Biodegradable microspheres for protein delivery. J Control Release 2003; 90(3): 261-80.
[http://dx.doi.org/10.1016/S0168-3659(03)00194-9] [PMID: 12880694]
[72]
Laffleur F. Mucoadhesive polymers for buccal drug delivery. Drug Dev Ind Pharm 2014; 40(5): 591-8.
[http://dx.doi.org/10.3109/03639045.2014.892959] [PMID: 24576266]
[73]
Mansuri S, Kesharwani P, Jain K, Tekade RK, Jain NK. Mucoadhesion: A promising approach in drug delivery system. React Funct Polym 2016; 100: 151-72.
[http://dx.doi.org/10.1016/j.reactfunctpolym.2016.01.011]
[74]
Garg NK, Mangal S, Khambete H, Tyagi RK. Mucosal delivery of vaccines: role of mucoadhesive/biodegradable polymers. Recent Pat Drug Deliv Formul 2010; 4(2): 114-28.
[http://dx.doi.org/10.2174/187221110791185015] [PMID: 20380624]
[75]
Kumar MR. Bakowsky, and CM Lehr. Biomaterials 2004; 25: 1771.
[76]
Cook MT, Tzortzis G, Charalampopoulos D, Khutoryanskiy VV. Microencapsulation of probiotics for gastrointestinal delivery. J Control Release 2012; 162(1): 56-67.
[http://dx.doi.org/10.1016/j.jconrel.2012.06.003] [PMID: 22698940]
[77]
Sakuma S, Hayashi M, Akashi M. Design of nanoparticles composed of graft copolymers for oral peptide delivery. Adv Drug Deliv Rev 2001; 47(1): 21-37.
[http://dx.doi.org/10.1016/S0169-409X(00)00119-8] [PMID: 11251243]
[78]
Kumar S, Dilbaghi N, Saharan R, Bhanjana G. Nanotechnology as emerging tool for enhancing solubility of poorly water-soluble drugs. Bionanoscience 2012; 2(4): 227-50.
[http://dx.doi.org/10.1007/s12668-012-0060-7]
[79]
Vaishya R, Khurana V, Patel S, Mitra AK. Long-term delivery of protein therapeutics. Expert Opin Drug Deliv 2015; 12(3): 415-40.
[http://dx.doi.org/10.1517/17425247.2015.961420] [PMID: 25251334]
[80]
Gueta O, Amiram M. Expanding the chemical repertoire of protein-based polymers for drug-delivery applications. Adv Drug Deliv Rev 2022; 190: 114460.
[http://dx.doi.org/10.1016/j.addr.2022.114460] [PMID: 36030987]
[81]
Farooq MA, Aquib M, Ghayas S, et al. Whey protein: A functional and promising material for drug delivery systems recent developments and future prospects. Polym Adv Technol 2019; 30(9): 2183-91.
[http://dx.doi.org/10.1002/pat.4676]
[82]
Lin YY, Chen CY, Ma DL, Leung CH, Chang CY, Wang HMD. Cell-derived artificial nanovesicle as a drug delivery system for malignant melanoma treatment. Biomed Pharmacother 2022; 147: 112586.
[http://dx.doi.org/10.1016/j.biopha.2021.112586] [PMID: 34999373]
[83]
Mousavizadeh A, Jabbari A, Akrami M, Bardania H. Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review. Colloids Surf B Biointerfaces 2017; 158: 507-17.
[http://dx.doi.org/10.1016/j.colsurfb.2017.07.012] [PMID: 28738290]
[84]
Solaro R, Chiellini F, Battisti A. Targeted delivery of protein drugs by nanocarriers. Materials (Basel) 2010; 3(3): 1928-80.
[http://dx.doi.org/10.3390/ma3031928]
[85]
Liu M, Fang X, Yang Y, Wang C. Peptide-enabled targeted delivery systems for therapeutic applications. Front Bioeng Biotechnol 2021; 9: 701504.
[http://dx.doi.org/10.3389/fbioe.2021.701504] [PMID: 34277592]
[86]
Kim TH, Lee S, Chen X. Nanotheranostics for personalized medicine. Expert Rev Mol Diagn 2013; 13(3): 257-69.
[http://dx.doi.org/10.1586/erm.13.15] [PMID: 23570404]
[87]
Giri NC. Protein and peptide drug delivery. Smart Drug Delivery 2022; 12: 39.
[88]
Veronese FM, Pasut G. PEGylation, successful approach to drug delivery. Drug Discov Today 2005; 10(21): 1451-8.
[http://dx.doi.org/10.1016/S1359-6446(05)03575-0] [PMID: 16243265]
[89]
Damodaran VB, Fee C. Protein PEGylation: An overview of chemistry and process considerations. European Pharmaceutical Review 2010; 15(1): 18-26.
[90]
Howard MD, Jay M, Dziubla TD, Lu X. PEGylation of nanocarrier drug delivery systems: state of the art. J Biomed Nanotechnol 2008; 4(2): 133-48.
[http://dx.doi.org/10.1166/jbn.2008.021]
[91]
Ye Q, Asherman J, Stevenson M, Brownson E, Katre NV. DepoFoam™ technology: a vehicle for controlled delivery of protein and peptide drugs. J Control Release 2000; 64(1-3): 155-66.
[http://dx.doi.org/10.1016/S0168-3659(99)00146-7] [PMID: 10640654]
[92]
Colletier JP, Chaize B, Winterhalter M, Fournier D. Protein encapsulation in liposomes: efficiency depends on interactions between protein and phospholipid bilayer. BMC Biotechnol 2002; 2(1): 9.
[http://dx.doi.org/10.1186/1472-6750-2-9] [PMID: 12003642]
[93]
Salehi B, Mishra AP, Nigam M, et al. Multivesicular liposome (Depofoam) in human diseases. Iran J Pharm Res 2020; 19(2): 9-21.
[PMID: 33224207]
[94]
Bulbake U, Doppalapudi S, Kommineni N, Khan W. Liposomal formulations in clinical use: an updated review. Pharmaceutics 2017; 9(4): 12.
[http://dx.doi.org/10.3390/pharmaceutics9020012] [PMID: 28346375]
[95]
Lagassé HAD, Alexaki A, Simhadri VL, et al. Recent advances in (therapeutic protein) drug development. F1000 Res 2017; 6: 113.
[http://dx.doi.org/10.12688/f1000research.9970.1] [PMID: 28232867]
[96]
Shimoni Eyal, et al. Oral delivery of proteins and peptides. US20160008290A1, 2016.
[97]
Chatterjee Deb, et al. Methods and compositions for protein delivery. US10577397B2, 2019.
[98]
Fang Ye, et al. Method and device for protein delivery into cells. US8288113B2, 2012.
[99]
Sung Hsing-Wen, et al. Nanoparticles for protein drug delivery. US20100330167A1, 2013.
[100]
Samir S. Transdermal protein delivery using low-frequency sonophoresis. US6002961A, 1999.
[101]
Morales JO, Fathe KR, Brunaugh A, et al. Challenges and future prospects for the delivery of biologics: oral mucosal, pulmonary, and transdermal routes. AAPS J 2017; 19(3): 652-68.
[http://dx.doi.org/10.1208/s12248-017-0054-z] [PMID: 28194704]
[102]
Richard J. Challenges in oral peptide delivery: lessons learnt from the clinic and future prospects. Ther Deliv 2017; 8(8): 663-84.
[http://dx.doi.org/10.4155/tde-2017-0024] [PMID: 28730934]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy