Development of composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles for sustained drug release  

作　　者：Ni Dong Chune Zhu Junhuang Jiang Di Huang Xing Li Guilan Quan Yang Liu Wen Tan Xin Pan Chuanbin Wu 

机构地区：[1]School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China [2]Institute of Biomedical and Pharmaceutical Sciences,Guangdong University of Technology,Guangzhou 510006,China [3]Shenyang Pharmaceutical University,Benxi 117004,China [4]College of Pharmacy,Chongqing Medical and Pharmaceutical College,Chongqing 401331,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2020年第3期347-355,共9页亚洲药物制剂科学（英文）

基　　金：the China Postdoctoral Science Foundation(Grant No.2016M602442);the Science and Technology Plan Projects of Guangdong Province(Grant No.2015B020232010);the 111 project(Grant No.B16047);the Natural Science Fund Project of Guangdong Province(Grant No.2018A030310555,Grant No.2016A030312013)。

摘　　要：This study aimed to prepare poly(D, L-lactic-co-glycolic acid) microspheres(PLGA-Ms)by a modified solid-in-oil-in-water(S/O/W) multi-emulsion technique in order to achieve sustained release with reduced initial burst and maintain efficient drug concentration for a prolonged period of time. Composite PLGA microspheres containing exenatideencapsulated lecithin nanoparticles(Ex-NPs-PLGA-Ms) were obtained by initial fabrication of exenatide-loaded lecithin nanoparticles(Ex-NPs) via the alcohol injection method,followed by encapsulation of Ex-NPs into PLGA microspheres. Compared to Ms prepared by the conventional water-in-oil-in-water(W/O/W) technique(Ex-PLGA-Ms), Ex-NPs-PLGAMs showed a more uniform particle size distribution, reduced initial burst release, and sustained release for over 60 d in vitro. Cytotoxicity studies showed that Ms prepared by both techniques had superior biocompatibility without causing any detectable cytotoxicity.In pharmacokinetic studies, the effective drug concentration was maintained for over 30 d following a single subcutaneous injection of two types of Ms formulation in rats, potentially prolonging the therapeutic action of Ex. In addition, administration of Ex-NPs-PLGA-Ms resulted in a more smooth plasma concentration-time profile with a higher area under the curve(AUC) compared to that of Ex-PLGA-Ms. Overall, Ex-NPs-PLGA-Ms prepared by the novel S/O/W method could be a promising sustained drug release system with reduced initial burst release and prolonged therapeutic efficacy.

关 键 词：MICROSPHERES PLGA PEPTIDES Lipid nanoparticles Sustained drug release 

分 类 号：R943[医药卫生—药剂学]