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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Research Article

Blending of PLGA-PEG-PLGA for Improving the Erosion and Drug Release Profile of PCL Microspheres

Author(s): Siyuan Wang, Xiaobo Feng, Ping Liu, Youxiu Wei* and Baojun Xiao*

Volume 21, Issue 11, 2020

Page: [1079 - 1087] Pages: 9

DOI: 10.2174/1389201021666200101104116

Price: $65

Abstract

Background: PCL has a long history as an industrialized biomaterial for preparing microspheres, but its hydrophobic property and slow degradation rate often cause drug degeneration, quite slow drug release rate and undesirable tri-phasic release profile.

Materials and Methods: In this study, we used the blending material of PLGA-PEG-PLGA and PCL to prepare microspheres. The microspheres degradation and drug release behaviors were evaluated through their molecular weight reduction rate, mass loss rate, morphology erosion and drug release profile. The hydrophilic PLGA-PEG-PLGA is expected to improve the degradation and drug release behaviors of PCL microspheres.

Results: Microspheres in blending materials exhibited faster erosion rates than pure PCL microspheres, forming holes much quickly on the particle’s surface for the drug to diffuse out. A higher proportion of PLGA-PEG-PLGA caused faster degradation and erosion rates. The blending microspheres showed much faster drug release rates than pure PCL microspheres.

Conclusion: With blending of 25wt% PLGA-PEG-PLGA, the release rate of microspheres speeded up significantly, while, with a further increase of PLGA-PEG-PLGA proportion (50%, 75%, 100%), it accelerated a little. The microspheres with PCL/PLGA-PEG-PLGA of 1/1 exhibited a linear-like drug release profile. The results could be a guideline for preparing microspheres based on blending materials to obtain a desirable release.

Keywords: Biodegradability, block copolymers, degradation, microsphere, erosion, release.

Graphical Abstract
[1]
Andhariya, J.V.; Choi, S.; Wang, Y.; Zou, Y.; Burgess, D.J.; Shen, J. Accelerated in vitro release testing method for naltrexone loaded PLGA microspheres. Int. J. Pharm., 2017, 520(1-2), 79-85.
[http://dx.doi.org/10.1016/j.ijpharm.2017.01.050] [PMID: 28153651]
[2]
Kojima, R.; Yoshida, T.; Tasaki, H.; Umejima, H.; Maeda, M.; Higashi, Y.; Watanabe, S.; Oku, N. Release mechanisms of tacrolimus-loaded PLGA and PLA microspheres and immunosuppressive effects of the microspheres in a rat heart transplantation model. Int. J. Pharm., 2015, 492(1-2), 20-27.
[http://dx.doi.org/10.1016/j.ijpharm.2015.07.004] [PMID: 26160668]
[3]
Dhanka, M.; Shetty, C.; Srivastava, R. Injectable methotrexate loaded polycaprolactone microspheres: Physicochemical characterization, biocompatibility, and hemocompatibility evaluation. Mater. Sci. Eng. C, 2017, 81, 542-550.
[http://dx.doi.org/10.1016/j.msec.2017.08.055] [PMID: 28888008]
[4]
Zhou, G.; Zhang, J.; Tai, J.; Han, Q.; Wang, L.; Wang, K.; Wang, S.; Fan, Y. Comparison of chitosan microsphere versus Ocarboxymethyl chitosan microsphere for drug delivery systems. J. Bioact. Compat. Polym. 2017, 088391151769075
[http://dx.doi.org/10.1177/0883911517690757]
[5]
Trouche, E.; Girod Fullana, S.; Mias, C.; Ceccaldi, C.; Tortosa, F.; Seguelas, M.H.; Calise, D.; Parini, A.; Cussac, D.; Sallerin, B. Evaluation of alginate microspheres for mesenchymal stem cell engraftment on solid organ. Cell Transplant., 2010, 19(12), 1623-1633.
[http://dx.doi.org/10.3727/096368910X514297] [PMID: 20719065]
[6]
Anderson, J.M.; Shive, M.S. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv. Drug Deliv. Rev., 2012, 64, 72-82.
[http://dx.doi.org/10.1016/j.addr.2012.09.004]
[7]
Chung, T.W.; Huang, Y.Y.; Liu, Y.Z. Effects of the rate of solvent evaporation on the characteristics of drug loaded PLLA and PDLLA microspheres. Int. J. Pharm., 2001, 212(2), 161-169.
[http://dx.doi.org/10.1016/S0378-5173(00)00574-3] [PMID: 11165073]
[8]
Li, H.; Wang, Q.; Xiao, Y.; Bao, C.; Li, W. 25-Hydroxyvitamin D(3)-loaded PLA microspheres: In vitro characterization and application in diabetic periodontitis models. AAPS PharmSciTech, 2013, 14(2), 880-889.
[http://dx.doi.org/10.1208/s12249-013-9978-5] [PMID: 23653087]
[9]
Feng, S.B.; Nie, L.; Zou, P.; Suo, J.P. effects of drug and polymer molecular weight on drug release from PLGA-MPEG microspheres. J. Appl. Polym. Sci., 2015, 132(6), 41431.
[http://dx.doi.org/10.1002/app.41431]
[10]
Alexandru, N.; Badila, E.; Weiss, E.; Cochior, D.; Stępień, E.; Georgescu, A. Vascular complications in diabetes: Microparticles and microparticle associated microRNAs as active players. Biochem. Biophys. Res. Commun., 2016, 472(1), 1-10.
[http://dx.doi.org/10.1016/j.bbrc.2016.02.038] [PMID: 26891868]
[11]
Schock, S.C.; Edrissi, H.; Burger, D.; Cadonic, R.; Hakim, A.; Thompson, C. Microparticles generated during chronic cerebral ischemia deliver proapoptotic signals to cultured endothelial cells. Biochem. Biophys. Res. Commun., 2014, 450(1), 912-917.
[http://dx.doi.org/10.1016/j.bbrc.2014.06.096] [PMID: 24976400]
[12]
Zheng, C-H.; Gao, J-Q.; Zhang, Y-P.; Liang, W-Q. A protein delivery system: Biodegradable alginate-chitosan-poly(lactic-co-glycolic acid) composite microspheres. Biochem. Biophys. Res. Commun., 2004, 323(4), 1321-1327.
[http://dx.doi.org/10.1016/j.bbrc.2004.09.007] [PMID: 15451441]
[13]
Mulia, K.; Witkamp, G.J.; Dawes, G.J.; Fratila-Apachitei, L.E.; Apachitei, I.; Duszczyk, J.; Pellikaan, H. Drug release from PLGA microspheres attached to solids using supercritical CO2. J. Biomater. Appl., 2011, 25(5), 401-412.
[http://dx.doi.org/10.1177/0885328209354365] [PMID: 20042430]
[14]
Guan, Y.; Li, X.; Zhang, X.; Cheng, Y.; Su, D.; Lu, C.; Fang, X.; Ma, Q.; Zhang, D.; Yu, H.; Hao, L.; Liu, S. Controlled delivery of growth-hormone-releasing peptide 6 from the poly(lactic-coglycolicacid)–poly(ethylene glycol)-poly(lactic-co-glycolic acid) copolymer and the effect of a growth-hormone-releasing peptide 6– copolymer hydrogel on the growth of rex rabbits. J. Appl. Polym. Sci. 2014, 131(9) n/a-n/a.
[15]
Wang, B.; Cao, Y.; Yang, L.; Wang, Y. Rheological properties of PLGA-PEG-PLGA copolymers for ophthalmic injection. J. Appl. Polym. Sci., 2012, 125(1), 370-375.
[http://dx.doi.org/10.1002/app.35584]
[16]
Zhou, S.; Liao, X.; Li, X.; Deng, X.; Li, H. Poly-D,L-lactide-co-poly(ethylene glycol) microspheres as potential vaccine delivery systems. J. Control. Release, 2003, 86(2-3), 195-205.
[http://dx.doi.org/10.1016/S0168-3659(02)00423-6] [PMID: 12526816]
[17]
Astete, C.E.; Sabliov, C.M. Synthesis and characterization of PLGA nanoparticles. J. Biomater. Sci. Polym. Ed., 2006, 17(3), 247-289.
[http://dx.doi.org/10.1163/156856206775997322] [PMID: 16689015]
[18]
Della Porta, G.; Falco, N.; Giordano, E.; Reverchon, E. PLGA microspheres by Supercritical Emulsion Extraction: A study on insulin release in myoblast culture. J. Biomater. Sci. Polym. Ed., 2013, 24(16), 1831-1847.
[http://dx.doi.org/10.1080/09205063.2013.807457] [PMID: 23786568]
[19]
Li, J.; Jiang, G.; Ding, F. Effects of polymer degradation on drug release from PLGA-mPEG microparticles: A dynamic study of microparticle morphological and physicochemical properties. J. Appl. Polym. Sci., 2008, 108(4), 2458-2466.
[http://dx.doi.org/10.1002/app.27823]
[20]
Mustafa, S.; Devi, V.K.; Pai, R.S. Effect of PEG and water-soluble chitosan coating on moxifloxacin-loaded PLGA long-circulating nanoparticles. Drug Deliv. Transl. Res., 2017, 7(1), 27-36.
[http://dx.doi.org/10.1007/s13346-016-0326-7] [PMID: 27576453]
[21]
Meng, F.T.; Ma, G.H.; Liu, Y.D.; Qiu, W.; Su, Z.G. Microencapsulation of bovine hemoglobin with high bio-activity and high entrapment efficiency using a W/O/W double emulsion technique. Colloids Surf. B Biointerfaces, 2004, 33(3-4), 177-183.
[http://dx.doi.org/10.1016/j.colsurfb.2003.10.003] [PMID: 15276634]
[22]
Yang, Y.Y.; Chung, T.S.; Ng, N.P. 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), 231-241.
[http://dx.doi.org/10.1016/S0142-9612(00)00178-2] [PMID: 11197498]
[23]
Hernán Pérez de la Ossa, D.; Ligresti, A.; Gil-Alegre, M.E.; Aberturas, M.R.; Molpeceres, J.; Di Marzo, V.; Torres Suárez, A.I. Poly-ε-caprolactone microspheres as a drug delivery system for cannabinoid administration: Development, characterization and in vitro evaluation of their antitumoral efficacy. J. Control. Release, 2012, 161(3), 927-932.
[http://dx.doi.org/10.1016/j.jconrel.2012.05.003] [PMID: 22580111]
[24]
Sandor, M.; Enscore, D.; Weston, P.; Mathiowitz, E. Effect of protein molecular weight on release from micron-sized PLGA microspheres. J. Control. Release, 2001, 76(3), 297-311.
[http://dx.doi.org/10.1016/S0168-3659(01)00446-1] [PMID: 11578744]
[25]
Cui, F.; Cun, D.; Tao, A.; Yang, M.; Shi, K.; Zhao, M.; Guan, Y. Preparation and characterization of melittin-loaded poly (DL-lactic acid) or poly (DL-lactic-co-glycolic acid) microspheres made by the double emulsion method. J. Control. Release, 2005, 107(2), 310-319.
[http://dx.doi.org/10.1016/j.jconrel.2005.07.001] [PMID: 16255081]

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