A Novel Method for Preparing Uniform-Sized PLGA Microspheres and the Application in Anti-tubercular Drug Delivery

Journal of Pharmaceutical Innovation - Tập 16 - Trang 620-629 - 2020
Huijia Lei1,2, Jinmiao Shi2, Xiqin Yang2, Jiangxue Li2, Heqiu Zhang2, Lingxia Zhang3, Zhiqiang Liu2
1Department of otorhinolaryngology, Beijing Jishuitan Hospital, Beijing, China
2Beijing Institute of Basic Medical Sciences, Beijing, China
3PLA Key Laboratory for Tuberculosis Control and Prevention /Beijing Key Laboratory of New Technologies for Tuberculosis Diagnosis and Treatment, The eighth medical center of Chinese PLA general hospital, Beijing, China

Tóm tắt

The size was a key factor influencing the drug loading, release, and delivery efficacies of poly (lactic-co-glycolic) acid (PLGA) microspheres (MS). The purpose of the study was to explore a novel and simple method to prepare uniform-sized PLGA MS for drug delivery. Different from routine homogenizer, a vortex shaker was employed for emulsification during the preparation of PLGA MS. To enhance the homogeneity of resulted PLGA MS, a glass bead was used to facilitate the emulsification. The size of PLGA MS was controlled by adjusting the working frequency and time of vortex shaker. Then, selective centrifugation was used to further enrich PLGA MS of desired size. The resulted PLGA MS were systematically evaluated in anti-tubercular drug delivery. Compared with the routine stirring-based method, the novel method possessed a higher efficiency of emulsification and resulted in more homogenous MS under similar conditions. The produced PLGA particles were of a narrow size distribution, which could be 1 to 5 μm by adjusting the working frequency and time of vortex shaker. The narrow size distribution made it rather easy to enrich PLGA MS of specific size through selective centrifugation. Then, to evaluate the potential of the PLGA MS for drug delivery, 2–3-μm sized PLGA MS were selected to deliver anti-tubercular drug rifampicin (RFP). In vitro experiments demonstrated that the loaded RFP could be well-controlled release and delivered into macrophages. Anti-tubercular experiments showed that the uniform-sized MS as carriers of RFP significantly enhanced the therapeutic efficacy of the drug. Collectively, the study provided a novel and simple method for preparing uniform-sized PLGA MS, which may be of potentially wide applications.

Tài liệu tham khảo

Jensen DK, Jensen LB, Koocheki S, Bengtson L, Cun D, Nielsen HM, et al. Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA. J Control Release. 2012;157(1):141–8. Harguindey A, Domaille DW, Fairbanks BD, Wagner J, Bowman CN, Cha JN. Synthesis and assembly of click-nucleic-acid-containing PEG-PLGA nanoparticles for DNA delivery. Adv Mater. 2017;29(24). Jeon SY, Park JS, Yang HN, Woo DG, Park KH. Co-delivery of SOX9 genes and anti-Cbfa-1 siRNA coated onto PLGA nanoparticles for chondrogenesis of human MSCs. Biomaterials. 2012;33(17):4413–23. Liu Q, Chen X, Jia J, Zhang W, Yang T, Wang L, et al. pH-responsive poly(D,L-lactic-co-glycolic acid) nanoparticles with rapid antigen release behavior promote immune response. ACS Nano. 2015;9(5):4925–38. Vyslouzil J, Dolezel P, Kejdusova M, Maskova E, Masek J, Lukac R, et al. Influence of different formulations and process parameters during the preparation of drug-loaded PLGA microspheres evaluated by multivariate data analysis. Acta Pharma. 2014;64(4):403–17. Patel NR, Damann K, Leonardi C, Sabliov CM. Size dependency of PLGA-nanoparticle uptake and antifungal activity against Aspergillus flavus. Nanomedicine (London). 2011;6(8):1381–95. Dawes GJ, Fratila-Apachitei LE, Mulia K, Apachitei I, Witkamp GJ, Duszczyk J. Size effect of PLGA spheres on drug loading efficiency and release profiles. J Mater Sci Mater Med. 2009;20(5):1089–94. Hirota K, Hasegawa T, Hinata H, Ito F, Inagawa H, Kochi C, et al. Optimum conditions for efficient phagocytosis of rifampicin-loaded PLGA microspheres by alveolar macrophages. J Control Release. 2007;119(1):69–76. Gaumet M, Gurny R, Delie F. Fluorescent biodegradable PLGA particles with narrow size distributions: preparation by means of selective centrifugation. Int J Pharm. 2007;342(1–2):222–30. Doan TV, Olivier JC. Preparation of rifampicin-loaded PLGA microspheres for lung delivery as aerosol by premix membrane homogenization. Int J Pharm. 2009;382(1–2):61–6. Liu R, Ma G, Meng FT, Su ZG. Preparation of uniform-sized PLA microcapsules by combining Shirasu porous glass membrane emulsification technique and multiple emulsion-solvent evaporation method. J Control Release. 2005;103(1):31–43. Liu Z, Li X, Xiu B, Duan C, Li J, Zhang X, et al. A novel and simple preparative method for uniform-sized PLGA microspheres: preliminary application in antitubercular drug delivery. Colloids Surf B: Biointerfaces. 2016;145:679–87. Chen X, Liu Y, Wang L, Zhang W, Fan B, Ma X, et al. Enhanced humoral and cell-mediated immune responses generated by cationic polymer-coated PLA microspheres with adsorbed HBsAg. Mol Pharm. 2014;11(6):1772–84. Makino K, Nakajima T, Shikamura M, Ito F, Ando S, Kochi C, et al. Efficient intracellular delivery of rifampicin to alveolar macrophages using rifampicin-loaded PLGA microspheres: effects of molecular weight and composition of PLGA on release of rifampicin. Colloids Surf B: Biointerfaces. 2004;36(1):35–42. Wei Q, Wei W, Lai B, Wang LY, Wang YX, Su ZG, et al. Uniform-sized PLA nanoparticles: preparation by premix membrane emulsification. Int J Pharm. 2008;359(1–2):294–7. Hirota K, Hasegawa T, Nakajima T, Inagawa H, Kohchi C, Soma G, et al. Delivery of rifampicin-PLGA microspheres into alveolar macrophages is promising for treatment of tuberculosis. J Control Release. 2010;142(3):339–46. Mezu-Ndubuisi OJ, Wang Y, Schoephoerster J, Falero-Perez J, Zaitoun IS, Sheibani N, et al. Intravitreal delivery of VEGF-A165-loaded PLGA microparticles reduces retinal vaso-obliteration in an in vivo mouse model of retinopathy of prematurity. Curr Eye Res. 2019;44(3):275–86. Khan I, Joshi G, Nakhate KT, Ajazuddin, Kumar R, Gupta U. Nano-co-delivery of berberine and anticancer drug using plga nanoparticles: exploration of better anticancer activity and in vivo kinetics. 2019;36(10):149. Zhu C, Yang H, Shen L, Zheng Z, Zhao S, Li Q, et al. Microfluidic preparation of PLGA microspheres as cell carriers with sustainable Rapa release. J Biomater Sci Polym Ed. 2019;30(9):737–55. Sydow K, Nikolenko H, Lorenz D, Muller RH, Dathe M. Lipopeptide-based micellar and liposomal carriers: influence of surface charge and particle size on cellular uptake into blood brain barrier cells. Eur J Pharm Biopharm. 2016;109:130–9. Lo CL, Chou MH, Lu PL, Lo IW, Chiang YT, Hung SY, et al. The effect of PEG-5K grafting level and particle size on tumor accumulation and cellular uptake. Int J Pharm. 2013;456(2):424–31. Huang J, Chen Z, Li Y, Li L, Zhang G. Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of cavitary pulmonary tuberculosis: preparation and in vitro characterization. Drug Des Devel Ther. 2017;11:585–92. O'Connor G, Krishnan N, Fagan-Murphy A, Cassidy J, O'Leary S, Robertson BD, et al. Inhalable poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating all-trans-retinoic acid (ATRA) as a host-directed, adjunctive treatment for Mycobacterium tuberculosis infection. Eur J Pharm Biopharm. 2019;134:153–65. Moin A, Raizaday A, Hussain T, Nagshubha B. Development and optimization of dual drugs (isoniazid and moxiflox-acin) loaded functional PLGA nanoparticles for the synergistic treatment of tuberculosis. Curr Drug Deliv. 2016;13(7):1034–52. Liu Z, Wang H, Wang Y, Lin Q, Yao A, Cao F, et al. The influence of chitosan hydrogel on stem cell engraftment, survival and homing in the ischemic myocardial microenvironment. Biomaterials. 2012;33(11):3093–106. Wang LY, Ma GH, Su ZG. Preparation of uniform sized chitosan microspheres by membrane emulsification technique and application as a carrier of protein drug. J Control Release. 2005;106(1–2):62–75.