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Recent Advances in Drug Delivery and Formulation

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ISSN (Print): 2667-3878
ISSN (Online): 2667-3886

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Mini-Review Article

Biodegradable Polymer-Based Microspheres for Depot Injection-Industry Perception

Author(s): Anand Kyatanwar, Mangal Nagarsenker and Bala Prabhakar*

Volume 17, Issue 1, 2023

Published on: 07 February, 2023

Page: [13 - 30] Pages: 18

DOI: 10.2174/2667387817666230119103126

Price: $65

Abstract

The discovery of proteins and peptides marked the actual beginning for pharmaceutical companies to do research on novel delivery systems for delivering these therapeutic proteins. Biodegradable polymer-based microspheres for controlled-release depot injection are known for decades and have proved to be one of the best possible approaches. Despite being known for decades, the commercial success of microsphere-based delivery systems remains limited. Very few products are seen in the market with no generics available for approved brand products whose patents have either expired or are about to expire. All this points to the complexities involved in developing these delivery systems. Still, many hurdles remain in developing these drug delivery systems namely, poor drug entrapment, unwanted burst release, poor in vitro in vivo correlation, lack of proper in vitro testing methods, problems involved during scale-up, and the most important hurdle being sterilization of the product. To achieve successful product development, all of these technical difficulties need to be simultaneously dealt with and resolved. This article attempts to highlight the problem areas for these delivery systems along with the regulatory requirements involved and map the present status of these delivery systems.

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[1]
Lee ACL, Harris JL, Khanna KK, Hong JH. A comprehensive review on current advances in peptide drug development and design. Int J Mol Sci 2019; 20(10): 2383.
[http://dx.doi.org/10.3390/ijms20102383] [PMID: 31091705]
[2]
Ibeanu N, Egbu R, Onyekuru L, et al. Injectables and depots to prolong drug action of proteins and peptides. Pharmaceutics 2020; 12(10): 1-42.
[http://dx.doi.org/10.3390/pharmaceutics12100999] [PMID: 33096803]
[3]
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]
[4]
Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology 2018; 16(1): 71.
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877]
[5]
Butreddy A, Gaddam RP, Kommineni N, Dudhipala N, Voshavar C. PLGA/PLA-based long-acting injectable depot microspheres in clinical use: Production and characterization overview for protein/peptide delivery. Int J Mol Sci 2021; 22(16): 8884.
[http://dx.doi.org/10.3390/ijms22168884] [PMID: 34445587]
[6]
Adepu S, Ramakrishna S. Controlled drug delivery systems: current status and future directions. Molecules 2021; 26(19): 5905.
[http://dx.doi.org/10.3390/molecules26195905] [PMID: 34641447]
[7]
Olusanya T, Haj Ahmad R, Ibegbu D, Smith J, Elkordy A. Liposomal drug delivery systems and anticancer drugs. Molecules 2018; 23(4): 907.
[http://dx.doi.org/10.3390/molecules23040907] [PMID: 29662019]
[8]
Burke G, Kenny E, Dalton M, et al. 1 Biodegradation and biodegradable polymers. In: Devine D, Ed. bioresorbable polymers; boston: Walter de Gruyter GmbH. 2019; pp. 1-16.
[http://dx.doi.org/10.1515/9783110640571-001]
[9]
Glaser A. Biological degradation of polymers in the environment. Plast Environ 2019; 2019: 85124.
[http://dx.doi.org/10.5772/intechopen.85124]
[10]
Namazi H. Polymers in our daily life. Bioimpacts 2017; 7(2): 73-4.
[http://dx.doi.org/10.15171/bi.2017.09] [PMID: 28752070]
[11]
Ni L, Chen H, Luo Z, Yu Y. Bioresorbable vascular stents and drug-eluting stents in treatment of coronary heart disease: a meta-analysis. J Cardiothorac Surg 2020; 15(1): 26.
[http://dx.doi.org/10.1186/s13019-020-1041-5] [PMID: 31992360]
[12]
Lee K, Silva EA, Mooney DJ. Growth factor delivery-based tissue engineering: general approaches and a review of recent developments. J R Soc Interface 2011; 8(55): 153-70.
[http://dx.doi.org/10.1098/rsif.2010.0223] [PMID: 20719768]
[13]
Scheiner KC, Maas-Bakker RF, van Steenbergen MJ, Schwendeman SP, Hennink WE, Kok RJ. Post-loading of proangiogenic growth factors in PLGA microspheres. Eur J Pharm Biopharm 2021; 158(158): 1-10.
[http://dx.doi.org/10.1016/j.ejpb.2020.10.022] [PMID: 33152482]
[14]
Sajid MS, McFall MR, Whitehouse PA, Sains PS. Systematic review of absorbable vs. non-absorbable sutures used for the closure of surgical incisions. World J Gastrointest Surg 2014; 6(12): 241-7.
[http://dx.doi.org/10.4240/wjgs.v6.i12.241] [PMID: 25548609]
[15]
U.S. Food & Drug Administration. Orange book: Approved drug products with therapeutic equivalence evaluations. Available from: https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm (Accessed on: Jun 1, 2022).
[16]
U.S. Food & Drug Administration. Inactive Ingredient Search for Approved Drug Products. Available from: https://www.accessdata. fda.gov/scripts/cder/iig/index.cfm (Accessed on: Jun 1, 2022).
[17]
Jem KJ, Tan B. The development and challenges of poly (lactic acid) and poly (glycolic acid). Adv Indus Eng Polym Res 2020; 3(2): 60-70.
[http://dx.doi.org/10.1016/j.aiepr.2020.01.002]
[18]
Balla E, Daniilidis V, Karlioti G, et al. Poly(lactic Acid): A versatile biobased polymer for the future with multifunctional properties—from monomer synthesis, polymerization techniques and molecular weight increase to PLA applications. Polymers (Basel) 2021; 13(11): 1822.
[http://dx.doi.org/10.3390/polym13111822] [PMID: 34072917]
[19]
Li C, Wang J, Wang Y, et al. Recent progress in drug delivery. Acta Pharm Sin B 2019; 9(6): 1145-62.
[http://dx.doi.org/10.1016/j.apsb.2019.08.003] [PMID: 31867161]
[20]
Sin LT, Tueen BS. Polylactic acid: A practical guide for the processing, manufacturing, and applications of PLA. (2nd ed.), Malaysia: Elsevier 2019.
[21]
USFDA. List of Drug Master Files (DMFs). Available from: https://www.fda.gov/drugs/drug-master-files-dmfs/list-drug-master-files-dmfs (Accessed on: Jun 1, 2022).
[22]
Wuisman PIJM, Smit TH. Bioresorbable polymers: heading for a new generation of spinal cages. Eur Spine J 2006; 15(2): 133-48.
[http://dx.doi.org/10.1007/s00586-005-1003-6] [PMID: 16292588]
[23]
Saalwächter K. Applications of NMR in polymer characterization - An introduction. In: Zhang R, Toshikazu Miyoshi PS, Eds. NMR methods for characterization of synthetic and natural polymers. Croydon 2019; pp. 1-22.
[http://dx.doi.org/10.1039/9781788016483-00001]
[24]
Izunobi JU, Higginbotham CL. Polymer molecular weight analysis by 1 H NMR spectroscopy. J Chem Educ 2011; 88(8): 1098-104.
[http://dx.doi.org/10.1021/ed100461v]
[25]
Sun J, Walker J, Beck-Broichsitter M, Schwendeman SP. Characterization of commercial PLGAs by NMR spectroscopy. Drug Deliv Transl Res 2022; 12(3): 720-9.
[http://dx.doi.org/10.1007/s13346-021-01023-3] [PMID: 34415565]
[26]
Li Y, Dang Y, Han D, et al. An Angiopep-2 functionalized nanoformulation enhances brain accumulation of tanshinone IIA and exerts neuroprotective effects against ischemic stroke. New J Chem 2018; 42(21): 17359-70.
[http://dx.doi.org/10.1039/C8NJ02441C]
[27]
Lagreca E, Onesto V, Di Natale C, La Manna S, Netti PA, Vecchione R. Recent advances in the formulation of PLGA microparticles for controlled drug delivery. Prog Biomater 2020; 9(4): 153-74.
[http://dx.doi.org/10.1007/s40204-020-00139-y] [PMID: 33058072]
[28]
Park H, Ha DH, Ha ES, Kim JS, Kim MS, Hwang SJ. Effect of stabilizers on encapsulation efficiency and release behavior of exenatide-loaded PLGA microsphere prepared by the W/O/W solvent evaporation method. Pharmaceutics 2019; 11(12): 627.
[http://dx.doi.org/10.3390/pharmaceutics11120627] [PMID: 31771254]
[29]
Zhou L, Shi H, Li Z, He C. Recent advances in complex coacervation design from macromolecular assemblies and emerging applications. Macromol Rapid Commun 2020; 41(21): 2000149.
[http://dx.doi.org/10.1002/marc.202000149] [PMID: 32431012]
[30]
Sing CE, Perry SL. Recent progress in the science of complex coacervation. Soft Matter 2020; 16(12): 2885-914.
[http://dx.doi.org/10.1039/D0SM00001A] [PMID: 32134099]
[31]
van der Kooij RS, Steendam R, Frijlink HW, Hinrichs WLJ. An overview of the production methods for core–shell microspheres for parenteral controlled drug delivery. Eur J Pharm Biopharm 2022; 170(170): 24-42.
[http://dx.doi.org/10.1016/j.ejpb.2021.11.007] [PMID: 34861359]
[32]
Galogahi FM, Zhu Y, An H, Nguyen NT. Core-shell microparticles: Generation approaches and applications. J Sci Adv Mater Devices 2020; 5(4): 417-35.
[http://dx.doi.org/10.1016/j.jsamd.2020.09.001]
[33]
Arpagaus C. PLA/PLGA nanoparticles prepared by nano spray drying. J Pharm Investig 2019; 49(4): 405-26.
[http://dx.doi.org/10.1007/s40005-019-00441-3]
[34]
Damiati SA, Damiati S. Microfluidic synthesis of indomethacin-loaded PLGA microparticles optimized by machine learning. Front Mol Biosci 2021; 8: 677547.
[http://dx.doi.org/10.3389/fmolb.2021.677547] [PMID: 34631792]
[35]
Rezvantalab S, Keshavarz Moraveji M. Microfluidic assisted synthesis of PLGA drug delivery systems. RSC Advances 2019; 9(4): 2055-72.
[http://dx.doi.org/10.1039/C8RA08972H] [PMID: 35516107]
[36]
Mares AG, Pacassoni G, Marti JS, Pujals S, Albertazzi L. Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology. PLoS One 2021; 16: 1-18.
[http://dx.doi.org/10.1371/journal.pone.0251821]
[37]
Gaikwad VL, Choudhari PB, Bhatia NM, Bhatia MS. Characterization of pharmaceutical nanocarriers: In vitro and in vivo studies. In: Grumez AM, Ed. nanomaterials for drug delivery and therapy. Cambridge: Elsevier Inc. 2019; pp. 33-58.
[http://dx.doi.org/10.1016/B978-0-12-816505-8.00016-3]
[38]
Danaei M, Dehghankhold M, Ataei S, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018; 10(2): 57.
[http://dx.doi.org/10.3390/pharmaceutics10020057] [PMID: 29783687]
[39]
Sarmadi M, Behrens AM, McHugh KJ, et al. Modeling, design, and machine learning-based framework for optimal injectability of microparticle-based drug formulations. Sci Adv 2020; 6(28): eabb6594.
[http://dx.doi.org/10.1126/sciadv.abb6594] [PMID: 32923598]
[40]
Garner J, Skidmore S, Park H, Park K, Choi S, Wang Y. A protocol for assay of poly(lactide-co-glycolide) in clinical products. Int J Pharm 2015; 495(1): 87-92.
[http://dx.doi.org/10.1016/j.ijpharm.2015.08.063] [PMID: 26319639]
[41]
Kim Y, Park EJ, Kim TW, Na DH. Recent progress in drug release testing methods of biopolymeric particulate system. Pharmaceutics 2021; 13(8): 1313.
[http://dx.doi.org/10.3390/pharmaceutics13081313] [PMID: 34452274]
[42]
Gu B, Burgess DJ. Prediction of dexamethasone release from PLGA microspheres prepared with polymer blends using a design of experiment approach. Int J Pharm 2015; 495(1): 393-403.
[http://dx.doi.org/10.1016/j.ijpharm.2015.08.089] [PMID: 26325309]
[43]
ICH Harmonised Guideline - Impurities: Guideline for Residual Solvents Q3C(R8). Available from: https://database.ich.org/sites/default/files/ICH_Q3C-R8_Guideline_Step4_2021_0422_1.pdf (Accessed on: Jun 1, 2022).
[44]
Park K, Otte A, Sharifi F, et al. Potential roles of the glass transition temperature of PLGA microparticles in drug release kinetics. Mol Pharm 2021; 18(1): 18-32.
[http://dx.doi.org/10.1021/acs.molpharmaceut.0c01089] [PMID: 33331774]
[45]
Kohno M, Andhariya JV, Wan B, et al. The effect of PLGA molecular weight differences on risperidone release from microspheres. Int J Pharm 2020; 582: 119339.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119339] [PMID: 32305366]
[46]
Stepto RFT. Dispersity in polymer science (IUPAC Recommendation 2009). Polym Int 2010; 59(1): 23-4.
[http://dx.doi.org/10.1002/pi.2748]
[47]
Manas D, Ovsik M, Mizera A, et al. The effect of irradiation on mechanical and thermal properties of selected types of polymers. Polymers (Basel) 2018; 10(2): 158.
[http://dx.doi.org/10.3390/polym10020158] [PMID: 30966194]
[48]
Harrell CR, Djonov V, Fellabaum C, Volarevic V. Risks of using sterilization by gamma radiation: The other side of the coin. Int J Med Sci 2018; 15(3): 274-9.
[http://dx.doi.org/10.7150/ijms.22644] [PMID: 29483819]
[49]
Sheena U, Parthiban KG, Selvakumar R. Lyophilized injection: a modern approach of injectable dosage form. J Drug Deliv Ther 2018; 8(5): 10-8.
[http://dx.doi.org/10.22270/jddt.v8i5.1829]
[50]
Burgess DJ, Crommelin DJA, Hussain AS, Chen ML. Assuring quality and performance of sustained and controlled release parenterals: EUFEPS workshop report. AAPS PharmSci 2004; 6(1): 100-11.
[http://dx.doi.org/10.1208/ps060111] [PMID: 15198512]
[51]
Cilurzo F, Selmin F, Minghetti P, et al. Injectability evaluation: an open issue. AAPS PharmSciTech 2011; 12(2): 604-9.
[http://dx.doi.org/10.1208/s12249-011-9625-y] [PMID: 21553165]
[52]
Dalzon B, Torres A, Reymond S, et al. Influences of nanoparticles characteristics on the cellular responses: The example of iron oxide and macrophages. Nanomaterials (Basel) 2020; 10(2): 266.
[http://dx.doi.org/10.3390/nano10020266] [PMID: 32033329]
[53]
Marante T, Viegas C, Duarte I, Macedo AS, Fonte P. An overview on spray-drying of protein-loaded polymeric nanoparticles for dry powder inhalation. Pharmaceutics 2020; 12(11): 1032.
[http://dx.doi.org/10.3390/pharmaceutics12111032] [PMID: 33137954]
[54]
Nick Pace C, Scholtz JM, Grimsley GR. Forces stabilizing proteins. FEBS Lett 2014; 588(14): 2177-84.
[http://dx.doi.org/10.1016/j.febslet.2014.05.006] [PMID: 24846139]
[55]
Yang Y, Chung TS, Ng NP. Morphology, drug distribution, and in vitro release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method. Biomaterials 2001; 22(3): 231-41.
[http://dx.doi.org/10.1016/S0142-9612(00)00178-2] [PMID: 11197498]
[56]
Khabiri M, Minofar B, Brezovský J, Damborský J, Ettrich R. Interaction of organic solvents with protein structures at protein-solvent interface. J Mol Model 2013; 19(11): 4701-11.
[http://dx.doi.org/10.1007/s00894-012-1507-z] [PMID: 22760789]
[57]
Ratanji KD, Derrick JP, Dearman RJ, Kimber I. Immunogenicity of therapeutic proteins: Influence of aggregation. J Immunotoxicol 2014; 11(2): 99-109.
[http://dx.doi.org/10.3109/1547691X.2013.821564] [PMID: 23919460]
[58]
Scheiblhofer S, Laimer J, Machado Y, Weiss R, Thalhamer J. Influence of protein fold stability on immunogenicity and its implications for vaccine design. Expert Rev Vaccines 2017; 16(5): 479-89.
[http://dx.doi.org/10.1080/14760584.2017.1306441] [PMID: 28290225]
[59]
U.S. Food and Drug Administration (FDA). Guidance for Industry: Immunogenicity assessment for therapeutic protein products. Available from: https://www.fda.gov/media/85017/download (Accessed on: Jun 1, 2022).
[60]
Zhao J, Wang L, Fan C, et al. Development of near zero-order release PLGA-based microspheres of a novel antipsychotic. Int J Pharm 2017; 516(1-2): 32-8.
[http://dx.doi.org/10.1016/j.ijpharm.2016.11.007] [PMID: 27825865]
[61]
Yang Z, Liu L, Su L, et al. Design of a zero-order sustained release PLGA microspheres for palonosetron hydrochloride with high encapsulation efficiency. Int J Pharm 2020; 575(575): 119006.
[http://dx.doi.org/10.1016/j.ijpharm.2019.119006] [PMID: 31899319]
[62]
Huang CL, Steele TWJ, Widjaja E, Boey FYC, Venkatraman SS, Loo JSC. The influence of additives in modulating drug delivery and degradation of PLGA thin films. NPG Asia Mater 2013; 5(7): e54.
[http://dx.doi.org/10.1038/am.2013.26]
[63]
Yoo J, Won YY. Phenomenology of the initial burst release of drugs from PLGA microparticles. ACS Biomater Sci Eng 2020; 6(11): 6053-62.
[http://dx.doi.org/10.1021/acsbiomaterials.0c01228] [PMID: 33449671]
[64]
Mayo J. Understanding the nutsche filtration and drying process process. Available from: http://www.ddpsinc.com/blog-0/understanding- the-nutsche-filtration-and-drying-process (Accessed on: Jun 1, 2022).
[65]
Smith PE. Third international conference on harmonization of technical requirements for registration of pharmaceuticals for human use--a toxicologist’s perspective. Toxicol Pathol 1996; 24(4): 519-28.
[http://dx.doi.org/10.1177/019262339602400423] [PMID: 8864198]
[66]
Rawat A, Burgess DJ. USP apparatus 4 method for in vitro release testing of protein loaded microspheres. Int J Pharm 2011; 409(1-2): 178-84.
[http://dx.doi.org/10.1016/j.ijpharm.2011.02.057] [PMID: 21376792]
[67]
Rodrigues de Azevedo C, von Stosch M, Costa MS, et al. Modeling of the burst release from PLGA micro- and nanoparticles as function of physicochemical parameters and formulation characteristics. Int J Pharm 2017; 532(1): 229-40.
[http://dx.doi.org/10.1016/j.ijpharm.2017.08.118] [PMID: 28867450]
[68]
Lee DS, Kang DW, Choi GW, Choi HG, Cho HY. Development of level a in vitro–vivo correlation for electrosprayed microspheres containing leuprolide: Physicochemical, pharmacokinetic, and pharmacodynamic evaluation. Pharmaceutics 2020; 12(1): 36.
[http://dx.doi.org/10.3390/pharmaceutics12010036] [PMID: 31906491]
[69]
Andhariya JV, Jog R, Shen J, et al. Development of Level A in vitro-in vivo correlations for peptide loaded PLGA microspheres. J Control Release 2019; 308: 1-13.
[http://dx.doi.org/10.1016/j.jconrel.2019.07.013] [PMID: 31301338]
[70]
Wang Y, Qu W, Choi SH. FDA’s regulatory science program for generic PLA/PLGA-based drug products. Am Pharm Rev 2016; 20: 4.
[71]
Guan Y, Wang L, Wang B, Ding M, Bao Y, Tan S. Recent advances of D-α-tocopherol polyethylene glycol 1000 Succinate based stimuli-responsive nanomedicine for cancer treatment. Curr Med Sci 2020; 40(2): 218-31.
[http://dx.doi.org/10.1007/s11596-020-2185-1] [PMID: 32337683]
[72]
Si W, Yang Q, Zong Y, et al. Toward understanding the effect of solvent evaporation on the morphology of PLGA microspheres by double emulsion method. Ind Eng Chem Res 2021; 60(25): 9196-205.
[http://dx.doi.org/10.1021/acs.iecr.1c00063]
[73]
Chung TW, Huang YY, Liu YZ. Effects of the rate of solvent evaporation on the characteristics of drug loaded PLLA and PDLLA microspheres. Int J Pharm 2001; 212(2): 161-9.
[http://dx.doi.org/10.1016/S0378-5173(00)00574-3] [PMID: 11165073]
[74]
Zhou FL, Chirazi A, Gough JE, Hubbard Cristinacce PL, Parker GJM. Hollow Polycaprolactone microspheres with/without a single surface hole by co-electrospraying. Langmuir 2017; 33(46): 13262-71.
[http://dx.doi.org/10.1021/acs.langmuir.7b01985] [PMID: 28901145]
[75]
Nyamweya NN. Applications of polymer blends in drug delivery. Future J Pharmaceut Sci 2021; 7(1): 18.
[http://dx.doi.org/10.1186/s43094-020-00167-2]
[76]
Liu Y, Ghassemi AH, Hennink WE, Schwendeman SP. The microclimate pH in poly(d,l-lactide-co-hydroxymethyl glycolide) microspheres during biodegradation. Biomaterials 2012; 33(30): 7584-93.
[http://dx.doi.org/10.1016/j.biomaterials.2012.06.013] [PMID: 22819499]
[77]
Li L, Schwendeman S P. Mapping neutral microclimate PH in PLGA microspheres. J Control Release 2005; 101(1-3 SPEC. ISS.): 163-73.
[http://dx.doi.org/10.1016/j.jconrel.2004.07.029]
[78]
Zolnik BS, Burgess DJ. Effect of acidic pH on PLGA microsphere degradation and release. J Control Release 2007; 122(3): 338-44.
[http://dx.doi.org/10.1016/j.jconrel.2007.05.034] [PMID: 17644208]
[79]
Allahyari M, Mohit E. Peptide/protein vaccine delivery system based on PLGA particles. Hum Vaccin Immunother 2016; 12(3): 806-28.
[http://dx.doi.org/10.1080/21645515.2015.1102804] [PMID: 26513024]
[80]
Bailey BA, Desai KGH, Ochyl LJ, Ciotti SM, Moon JJ, Schwendeman SP. Self-encapsulating Poly(lactic- co -glycolic acid) (PLGA) microspheres for intranasal vaccine delivery. Mol Pharm 2017; 14(9): 3228-37.
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00586] [PMID: 28726424]
[81]
Woo BH, Jiang G, Jo YW, DeLuca PP. Preparation and characterization of a composite PLGA and poly(acryloyl hydroxyethyl starch) microsphere system for protein delivery. Pharm Res 2001; 18(11): 1600-6.
[http://dx.doi.org/10.1023/A:1013090700443] [PMID: 11758769]
[82]
Zhao J, Guo B, Ma PX. Injectable alginate microsphere/PLGA–PEG–PLGA composite hydrogels for sustained drug release. RSC Advances 2014; 4(34): 17736-42.
[http://dx.doi.org/10.1039/c4ra00788c]
[83]
van Manen H-J, van Apeldoorn AA, Verrijk R, van Blitterswijk CA, Otto C. Intracellular degradation of microspheres based on cross-linked dextran hydrogels or amphiphilic block copolymers: a comparative raman microscopy study. Int J Nanomedicine 2007; 2(2): 241-52.
[http://dx.doi.org/10.2217/17435889.2.2.241] [PMID: 17722552]
[84]
Huang S, Huang G. Preparation and drug delivery of dextran-drug complex. Drug Deliv 2019; 26(1): 252-61.
[http://dx.doi.org/10.1080/10717544.2019.1580322] [PMID: 30857442]
[85]
Daily MED. National Library of Medicine. Available from: https://dailymed.nlm.nih.gov/dailymed/index.cfm (Accessed on: Jun 1, 2022).
[86]
De La Vega JC, Elischer P, Schneider T, Häfeli UO. Uniform polymer microspheres: monodispersity criteria, methods of formation and applications. Nanomedicine (Lond) 2013; 8(2): 265-85.
[http://dx.doi.org/10.2217/nnm.12.210] [PMID: 23394156]
[87]
Blazejewski Emile. Method of preparing microparticles by double emulsion. Patent WO 2019/066649 A1 2018.
[88]
Jo YW, Woo BH, Hazrati AM, DeLuca PP. Use of Pharmasep unit for processing micropheres Available from: http://www.pharms citech.com/ (Accessed on: Jun 1, 2022).
[http://dx.doi.org/10.1208/pt0201_tn2]
[89]
Cakir-Koc R, Budama-Kilinc Y, Kokcu Y, Kecel-Gunduz S. Docking of immunogenic peptide of toxoplasma gondii and encapsulation with polymer as vaccine candidate. Artif Cells Nanomed Biotechnol 2018; 46(sup2): 744-54.
[http://dx.doi.org/10.1080/21691401.2018.1469024]
[90]
Mohan DG, Gopi S, Rajasekar V, et al. Investigation of the interactions between melittin and the PLGA and PLA polymers: molecular dynamic simulation and binding free energy calculation. Mater Today Proc 2019; 27: 31.
[http://dx.doi.org/10.1080/14484846.2018.1432089]
[91]
U.S. Food & Drug Administration (FDA). Container closure systems for packaging human drugs and biologics: Chemistry, manufacturing, and controls documentation. Available from: http://www.fda.gov/cder/guidance/index.htm (Accessed on: Jun 1, 2022).
[92]
Krayukhina E, Tsumoto K, Uchiyama S, Fukui K. Effects of syringe material and silicone oil lubrication on the stability of pharmaceutical proteins. J Pharm Sci 2015; 104(2): 527-35.
[http://dx.doi.org/10.1002/jps.24184] [PMID: 25256796]
[93]
Chisholm CF, Baker AE, Soucie KR, Torres RM, Carpenter JF, Randolph TW. Silicone oil microdroplets can induce antibody responses against recombinant murine growth hormone in mice. J Pharm Sci 2016; 105(5): 1623-32.
[http://dx.doi.org/10.1016/j.xphs.2016.02.019] [PMID: 27020987]
[94]
U.S. Food & Drug Administration (FDA). Complex drug products. Available from: https://www.fda.gov/media/113539/download (Accessed on: Jun 1, 2022).

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