Acta Chimica Sinica ›› 2015, Vol. 73 ›› Issue (1): 60-65.DOI: 10.6023/A14110767 Previous Articles    

Article

聚(L-谷氨酸)微球的制备及其口服药物控释研究

赵丽b, 丁建勋a, 肖春生a, 陈学思a, 盖广清b, 王立艳c   

  1. a 中国科学院长春应用化学研究所 中国科学院生态环境高分子材料重点实验室 长春 130022;
    b 吉林建筑大学 建筑节能技术工程实验室 长春 130118;
    c 吉林建筑大学 材料科学与工程学院 长春 130118
  • 收稿日期:2014-11-09 出版日期:2015-01-14 发布日期:2015-01-06
  • 通讯作者: 肖春生 E-mail:xiaocs@ciac.ac.cn
  • 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

Zhao Lib, Ding Jianxuna, Xiao Chunshenga, Chen Xuesia, Gai Guangqingb, Wang Liyanc   

  1. a Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022;
    b Laboratory of Building Energy-Saving Technology Engineering, Jilin Jianzhu University, Changchun 130118;
    c College of Material Science and Engineering, Jilin Jianzhu University, Changchun 130118
  • Received:2014-11-09 Online:2015-01-14 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).

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.

Key words: enteric carrier, poly(L-glutamic acid), oral administration, microsphere, drug delivery