聚(L-谷氨酸)微球的制备及其口服药物控释研究
收稿日期: 2014-11-09
网络出版日期: 2015-01-06
基金资助
项目受国家自然科学基金(Nos. 51403075, 51303174, 51203153, 51390484, 51233004, 51321062)及吉林省科技发展计划基金(No. 20140520050JH)资助.
Poly(L-glutamic acid) Microsphere: Preparation and Application in Oral Drug Controlled Release
Received date: 2014-11-09
Online published: 2015-01-06
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 51403075, 51303174, 51203153, 51390484, 51233004, 51321062) and the Scientific Development Program of Jilin Province (No. 20140520050JH).
通过正己胺引发γ-苯甲基-L-谷氨酸酯-N-内羧酸酐(BLG-NCA)开环聚合制备聚(γ-苯甲基-L-谷氨酸酯)(PBLG), 并进一步脱掉苯甲基保护得到聚(L-谷氨酸)(PLG). 以利福平为模型药物, 通过油包油(O/O)无水乳液法制备了PLG载药微球. 扫描电子显微镜检测表明该载药微球具有良好的球形形貌且粒径分布较均一, 粒径大小约为9.0 μm. 体外释放实验表明该载药微球对利福平的释放具有明显的pH敏感性, 在模拟胃液中较少释放利福平, 而在模拟肠液中较快并大量释放利福平, 符合口服药物载体释放性能的要求, 可用于口服药物的定位肠溶性载体. 此外, 噻唑蓝实验表明该微球具有良好的生物相容性.
赵丽 , 丁建勋 , 肖春生 , 陈学思 , 盖广清 , 王立艳 . 聚(L-谷氨酸)微球的制备及其口服药物控释研究[J]. 化学学报, 2015 , 73(1) : 60 -65 . DOI: 10.6023/A14110767
Poly(L-glutamic acid) (PLG) and its derivatives, which are biodegradable and biocompatible, are one kind of the most widely investigated synthetic polypeptides as biomedical materials benefited from their pH-responsive property (pKa～4.1) and modifiable side carboxyl group. In this work, PLG was synthesized via a two-step procedure. Poly(γ-benzyl-L-glutamate) (PBLG) was first synthesized by the ring-opening polymerization of γ-benzyl-L-glutamate-N-carboxyanhydride (BLG-NCA) using n-hexylamine as initiator, and then PLG was prepared by the deprotection of benzyl groups in PBLG. PLG microsphere was prepared by the oil-in-oil (O/O) anhydrous emulsion method utilizing N,N-dimetylformamide as an inner oil phase and corn oil as an outer oil phase. Rifampicin, a model drug, was loaded into the PLG microsphere, and the drug loading capacity and entrapment efficiency were revealed. The scanning electron microscopy micrograph indicated that the drug-loaded microsphere exhibited spherical morphology with narrow size distribution and average diameter at about 9.0 μm. To investigate the application of PLG microsphere in oral drug delivery (especially for enteric-coated drugs), the in vitro rifampicin release experiments in simulated gastric or intestinal fluid were performed. In vitro release results revealed that the release of rifampicin from microsphere was highly dependent on pH. In detail, less amount of rifampicin was released in simulated gastric fluid, while the quicker release of rifampicin occurred in simulated intestinal fluid. It was because that the deprotonation of carboxyl groups in PLG caused the loose, expansion, and even disintegration of PLG microsphere in simulated intestinal fluid. Moreover, the morphology of microsphere in simulated gastric fluid was different from that in simulated intestinal fluid, which further confirmed the pH-sensitive property of microsphere. Additionally, in vitro methyl thiazolyl tetrazolium assays demonstrated that the PLG microsphere was biocompatible. Therefore, the biocompatible PLG microsphere with the intelligent pH-triggered drug release should be promising for application in oral drug delivery.
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