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Pharmaceutical Nanotechnology

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

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Research Article

Computer Optimization of Stealth Biodegradable Polymeric Dual-loaded Nanoparticles for Cancer Therapy Using Central Composite Face-centered Design

Author(s): Yvonne A. Berko and Emmanuel O. Akala*

Volume 8, Issue 2, 2020

Page: [108 - 132] Pages: 25

DOI: 10.2174/2211738508666200224110410

Price: $65

Abstract

Background: Combination chemotherapy capable of overcoming cancer drug resistance can be facilitated by nanotechnology.

Objective: Synthesis, characterization, statistical experimental design, analysis and optimization of stealth pH-sensitive polymeric nanoparticles suitable as a platform for simultaneous delivery of paclitaxel and 17-AAG in breast cancer therapy were investigated.

Methods: An acetal crosslinker and a poly(ɛ)caprolactone macromonomer were synthesized and characterized. The statistical experimental design used was the response surface method (RSM). We used the central composite face-centered design (CCF) in three independent factors and seventeen runs. Nanoparticles were fabricated by dispersion polymerization techniques. Response variables evaluated were: particle size, drug loading, encapsulation efficiency, and in vitro availability.

Results: Scanning electron micrographs showed the formation of spherical nanoparticles. Computer software was used for the analysis of variance with a 95% confidence level and Q2 (goodness of prediction) to select an appropriate model for each of the response variables. Each term in each of the models was tested for the significance of the regression coefficients. The computer software optimizer was used for optimization to select factor combination to minimize particle size, time (h) for maximum release of paclitaxel and 17-AAG, to maximize paclitaxel and 17-AAG loading efficiency and to maximize paclitaxel and 17-AAG encapsulation efficiency.

Conclusion: The optimization was successful, as shown by the validation data which lie within the confidence intervals of predicted values of the response variables. The selected factor combination is suitable for the in vivo evaluation of the nanoparticles loaded with paclitaxel and 17-AAG.

Keywords: Computer optimization, dispersion polymerization, pH-responsive crosslinker, poly(ɛ) caprolactone macromonomer, polymeric nanoparticles, statistical experimental design.

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[1]
Fisusi FA, Akala EO. Drug combinations in breast cancer therapy. Pharm Nanotechnol 2019; 7(1): 3-23.
[http://dx.doi.org/10.2174/2211738507666190122111224] [PMID: 30666921]
[2]
Giordano SH. Update on locally advanced breast cancer. Oncologist 2003; 8(6): 521-30.
[http://dx.doi.org/10.1634/theoncologist.8-6-521] [PMID: 14657530]
[3]
Wang M, Hou L, Chen M, et al. Neoadjuvant chemotherapy creates surgery opportunities for inoperable locally advanced breast cancer. Sci Rep 2017; 7: 44673.
[http://dx.doi.org/10.1038/srep44673] [PMID: 28327615]
[4]
Pronzato P, Rondini M. First line chemotherapy of metastatic breast cancer Annals of Oncology 2006; 17(suppl_5): v165-8.
[http://dx.doi.org/10.1093/annonc/mdj974]
[5]
Chou T-C. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 2006; 58(3): 621-81.
[http://dx.doi.org/10.1124/pr.58.3.10] [PMID: 16968952]
[6]
Foucquier J, Guedj M. Analysis of drug combinations: current methodological landscape. Pharmacol Res Perspect 2015; 3(3) e00149
[http://dx.doi.org/10.1002/prp2.149] [PMID: 26171228]
[7]
Anampa J, Makower D, Sparano JA. Progress in adjuvant chemotherapy for breast cancer: an overview. BMC Med 2015; 13(1): 195-45.
[8]
Keith CT, Borisy AA, Stockwell BR. Multicomponent therapeutics for networked systems. Nat Rev Drug Discov 2005; 4(1): 71-8.
[http://dx.doi.org/10.1038/nrd1609] [PMID: 15688074]
[9]
Davoli A, Hocevar BA, Brown TL. Progression and treatment of HER2-positive breast cancer. Cancer Chemother Pharmacol 2010; 65(4): 611-23.
[http://dx.doi.org/10.1007/s00280-009-1208-1] [PMID: 20087739]
[10]
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344(11): 783-92.
[http://dx.doi.org/10.1056/NEJM200103153441101] [PMID: 11248153]
[11]
Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002; 20(3): 719-26.
[http://dx.doi.org/10.1200/JCO.20.3.719] [PMID: 11821453]
[12]
Lan KH, Lu CH, Yu D. Mechanisms of trastuzumab resistance and their clinical implications. Ann N Y Acad Sci 2005; 1059: 70-5.
[http://dx.doi.org/10.1196/annals.1339.026] [PMID: 16382045]
[13]
Morrow PK, Zambrana F, Esteva FJ, Esteva FJ. Recent advances in systemic therapy: Advances in systemic therapy for HER2-positive metastatic breast cancer. Breast Cancer Res 2009; 11(4): 207-16.
[http://dx.doi.org/10.1186/bcr2324] [PMID: 19664181]
[14]
Milani A, Montemurro F, Gioeni L, Aglietta M, Valabrega G. Role of trastuzumab in the management of HER2-positive metastatic breast cancer. Breast Cancer (Dove Med Press) 2010; 2: 93-109.
[PMID: 24367170]
[15]
Blackwell KL, Burstein HJ, Storniolo AM, et al. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol 2010; 28(7): 1124-30.
[16]
Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006; 355(26): 2733-43.
[http://dx.doi.org/10.1056/NEJMoa064320] [PMID: 17192538]
[17]
Nahta R, Shabaya S, Ozbay T, Rowe DL. Personalizing HER2-targeted therapy in metastatic breast cancer beyond HER2 status: what we have learned from clinical specimens. Curr Pharmacogenomics Person Med 2009; 7(4): 263-74.
[http://dx.doi.org/10.2174/187569209790112337] [PMID: 20300449]
[18]
Perez EA, Suman VJ, Davidson NE, et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol 2011; 29(34): 4491-7.
[http://dx.doi.org/10.1200/JCO.2011.36.7045] [PMID: 22042958]
[19]
Garcia AG, Nedev H, Bijian K, Su J, Alaoui-Jamali MA, Saragovi HU. Reduced in vivo lung metastasis of a breast cancer cell line after treatment with Herceptin mAb conjugated to chemotherapeutic drugs. Oncogene 2012; 32(20): 2527-33.
[PMID: 22797066]
[20]
Lewis Phillips GD, Li G, Dugger DL, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res 2008; 68(22): 9280-90.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-1776] [PMID: 19010901]
[21]
Barok M, Tanner M, Köninki K, Isola J. Trastuzumab-DM1 causes tumour growth inhibition by mitotic catastrophe in trastuzumab-resistant breast cancer cells in vivo. Breast Cancer Res 2011; 13(2): R46.
[http://dx.doi.org/10.1186/bcr2868] [PMID: 21510863]
[22]
Webb S. Pharma interest surges in antibody drug conjugates. Nat Biotechnol 2011; 29(4): 297-8.
[http://dx.doi.org/10.1038/nbt0411-297] [PMID: 21478833]
[23]
Guha M. T-DM1 impresses at ASCO. Nat Biotechnol 2012; 30(8): 728.
[http://dx.doi.org/10.1038/nbt0812-728]
[24]
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100(1): 57-70.
[http://dx.doi.org/10.1016/S0092-8674(00)81683-9] [PMID: 10647931]
[25]
Davenport J, Balch M, Galam L, et al. High-throughput screen of natural product libraries for hsp90 inhibitors. Biology 2014; 3: 101-38.
[26]
Kamal A, Thao L, Sensintaffar J, et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 2003; 425(6956): 407-10.
[http://dx.doi.org/10.1038/nature01913] [PMID: 14508491]
[27]
De Mattos-Arruda L, Cortes J. Breast cancer and HSP90 inhibitors: is there a role beyond the HER2-positive subtype? Breast 2012; 21(4): 604-7.
[http://dx.doi.org/10.1016/j.breast.2012.04.002] [PMID: 22560618]
[28]
O’Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006; 66(3): 1500-8.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-2925] [PMID: 16452206]
[29]
Carracedo A, Ma L, Teruya-Feldstein J, et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest 2008; 118(9): 3065-74.
[http://dx.doi.org/10.1172/JCI34739] [PMID: 18725988]
[30]
Porter JR, Fritz CC, Depew KM. Discovery and development of Hsp90 inhibitors: a promising pathway for cancer therapy. Curr Opin Chem Biol 2010; 14(3): 412-20.
[http://dx.doi.org/10.1016/j.cbpa.2010.03.019] [PMID: 20409745]
[31]
Modi S, Stopeck AT, Gordon MS, et al. Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study. J Clin Oncol 2007; 25(34): 5410-7.
[http://dx.doi.org/10.1200/JCO.2007.11.7960] [PMID: 18048823]
[32]
Lu X, Xiao L, Wang L, Ruden DM. Hsp90 inhibitors and drug resistance in cancer: the potential benefits of combination therapies of Hsp90 inhibitors and other anti-cancer drugs. Biochem Pharmacol 2012; 83(8): 995-1004.
[http://dx.doi.org/10.1016/j.bcp.2011.11.011] [PMID: 22120678]
[33]
Trepel J, Mollapour M, Giaccone G, Neckers L. Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer 2010; 10(8): 537-49.
[http://dx.doi.org/10.1038/nrc2887] [PMID: 20651736]
[34]
Mahalingam D, Swords R, Carew JS, Nawrocki ST, Bhalla K, Giles FJ. Targeting HSP90 for cancer therapy. Br J Cancer 2009; 100(10): 1523-9.
[http://dx.doi.org/10.1038/sj.bjc.6605066] [PMID: 19401686]
[35]
Pilpel Y, Sudarsanam P, Church GM. Identifying regulatory networks by combinatorial analysis of promoter elements. Nat Genet 2001; 29(2): 153-9.
[http://dx.doi.org/10.1038/ng724] [PMID: 11547334]
[36]
Lee SH, Hayano K, Zhu AX, Sahani DV, Yoshida H. Advanced hepatocellular carcinoma: perfusion computed tomography-based kinetic parameter as a prognostic biomarker for prediction of patient survival. J Comput Assist Tomogr 2015; 39(5): 687-96.
[http://dx.doi.org/10.1097/RCT.0000000000000288] [PMID: 26222909]
[37]
Hu C-MJ, Zhang L. Nanoparticle-based combination therapy toward overcoming drug resistance in cancer. Biochem Pharmacol 2012; 83(8): 1104-11.
[http://dx.doi.org/10.1016/j.bcp.2012.01.008] [PMID: 22285912]
[38]
Münster PN, Basso A, Solit D, Norton L, Rosen N. Modulation of Hsp90 function by ansamycins sensitizes breast cancer cells to chemotherapy-induced apoptosis in an RB- and schedule-dependent manner. See: E. A. Sausville, Combining cytotoxics and 17-allylamino, 17-demethoxygeldanamycin: sequence and tumor biology matters Clin Cancer Res 2001; 7: 2155-8.
[PMID: 11489796]
[39]
Puri R, Berhe SA, Akala EO. pH-sensitive polymeric nanoparticles fabricated by dispersion polymerization for the delivery of bioactive agents. Pharm Nanotechnol 2017; 5(1): 44-66.
[http://dx.doi.org/10.2174/2211738505666170110102320] [PMID: 28948910]
[40]
Ogunwuyi O, Adesina S, Akala EO. D-Optimal mixture experimental design for stealth biodegradable crosslinked docetaxel-loaded poly-ε-caprolactone nanoparticles manufactured by dispersion polymerization. Pharmazie 2015; 70(3): 165-76.
[PMID: 25980177]
[41]
Derringer G, Suich R. Simultaneous optimization of several response variables. J Qual Technol 1980; 12(4): 214-9.
[http://dx.doi.org/10.1080/00224065.1980.11980968]
[42]
Akala EO, Adesina S, Ogunwuyi O. Computer optimization of biodegradable nanoparticles fabricated by dispersion polymerization. Int J Environ Res Public Health 2015; 13(1) h13010047
[http://dx.doi.org/10.3390/ijerph13010047] [PMID: 26703678]
[43]
Fenech A, Fearn T, Strlic M. Use of design-of-experiment principles to develop a dose-response function for color photographs. Polym Degrad Stabil 2012; 97: 621-5.
[http://dx.doi.org/10.1016/j.polymdegradstab.2012.01.012]
[44]
Box G, Hunter J, Hunter W. Statistics for Experimenters; design, innovation, and discovery. 2nd ed. Wiley: United States 2005; p. 672.
[45]
Boguslavsky L, Baruch S, Margel S. Synthesis and characterization of polyacrylonitrile nanoparticles by dispersion/emulsion polymerization process. J Colloid Interface Sci 2005; 289(1): 71-85.
[http://dx.doi.org/10.1016/j.jcis.2005.03.063] [PMID: 16009219]
[46]
Shen S, Sudol ED, El‐Aasser MS. Dispersion polymerization of methyl methacrylate: mechanism of particle formation. Int J Polym Sci 1994; 32(6)
[47]
Adesina SK, Wight SA, Akala EO. Optimization of the fabrication of novel stealth PLA-based nanoparticles by dispersion polymerization using D-optimal mixture design. Drug Dev Ind Pharm 2014; 40(11): 1547-56.
[http://dx.doi.org/10.3109/03639045.2013.838578] [PMID: 24059281]
[48]
Xia XJ, Peng J, Zhang PX, Jin DJ, Liu YL. Validated HPLC method for the determination of paclitaxel-related substances in an intravenous emulsion loaded with a paclitaxel-cholesterol complex. Indian J Pharm Sci 2013; 75(6): 672-9.
[PMID: 24591742]
[49]
Guo W, Reigan P, Siegel D, Zirrolli J, Gustafson D, Ross D. Formation of 17-allylamino-demethoxygeldanamycin (17-AAG) hydroquinone by NAD(P)H:quinone oxidoreductase 1: role of 17-AAG hydroquinone in heat shock protein 90 inhibition. Cancer Res 2005; 65(21): 10006-15.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-2029] [PMID: 16267026]
[50]
Pradhan R, Poudel BK, Choi JY, et al. Erratum to: Preparation and evaluation of 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) nanoparticles. Arch Pharm Res 2015; 38(5): 930-1.
[http://dx.doi.org/10.1007/s12272-014-0463-9] [PMID: 25098423]
[51]
Kato Y, Ozawa S, Miyamoto C, et al. Acidic extracellular microenvironment and cancer. Cancer Cell Int 2013; 13(1): 89.
[http://dx.doi.org/10.1186/1475-2867-13-89] [PMID: 24004445]
[52]
Hu YB, Dammer EB, Ren RJ, Wang G. The endosomal-lysosomal system: from acidification and cargo sorting to neurodegeneration. Transl Neurodegener 2015; 4: 18.
[http://dx.doi.org/10.1186/s40035-015-0041-1] [PMID: 26448863]
[53]
Kamaly N, Yameen B, Wu J, Farokhzad OC. Degradable controlled-release polymers and polymeric nanoparticles: mechanisms of controlling drug release. Chem Rev 2016; 116(4): 2602-63.
[http://dx.doi.org/10.1021/acs.chemrev.5b00346] [PMID: 26854975]
[54]
Hoo CM, Starostin N, West P, Mecartney ML. A comparison of atomic force microscopy (AFM) and dynamic light scattering (DLS) methods to characterize nanoparticle size distributions. J Nanopart Res 2008; 10(1): 89-96.
[http://dx.doi.org/10.1007/s11051-008-9435-7]
[55]
Kashi TS, Eskandarion S, Esfandyari-Manesh M, et al. Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method. Int J Nanomedicine 2012; 7: 221-34.
[PMID: 22275837]
[56]
Chen B, Dai W, He B, et al. Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment. Theranostics 2017; 7(3): 538-58.
[http://dx.doi.org/10.7150/thno.16684] [PMID: 28255348]
[57]
Koren E, Apte A, Jani A, Torchilin VP. Multifunctional PEGylated 2C5-immunoliposomes containing pH-sensitive bonds and TAT peptide for enhanced tumor cell internalization and cytotoxicity. J Control Release 2012; 160(2): 264-73.
[http://dx.doi.org/10.1016/j.jconrel.2011.12.002] [PMID: 22182771]
[58]
Patil S, Sandberg A, Heckert E, Self W, Seal S. Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential. Biomaterials 2007; 28(31): 4600-7.
[http://dx.doi.org/10.1016/j.biomaterials.2007.07.029] [PMID: 17675227]
[59]
Obeso-Vera C, Cornejo-Bravo JM, Serrano-Medina A, Licea-Claverie A. Effect of crosslinkers on size and temperature sensitivity of poly(N-isopropylacryl-amide) microgels. Polym Bull 2013; 70(2): 653-64.
[http://dx.doi.org/10.1007/s00289-012-0832-9]
[60]
Atyabi F, Manoochehri S, Moghadam SH, Dinarvand R. Cross-linked starch microspheres: effect of cross-linking condition on the microsphere characteristics. Arch Pharm Res 2006; 29(12): 1179-86.
[http://dx.doi.org/10.1007/BF02969311] [PMID: 17225470]
[61]
Aravand MA, Semsarzadeh MA. particle formation by emulsion inversion method: effect of the stirring speed on inversion and formation of spherical particles. Macromol Symp 2008; 274: 141-7.
[http://dx.doi.org/10.1002/masy.200851419]

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