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含胰岛素-月桂醇硫酸酯复合物的高载药量聚乳酸-羟基乙酸共聚物纳米粒的优化配方

Optimized formulation of high-payload PLGA nanoparticles containing insulin-lauryl sulfate complex.

作者信息

Shi Kai, Cui Fude, Yamamoto Hiromitsu, Kawashima Yoshiaki

机构信息

Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, Shenyang, China.

出版信息

Drug Dev Ind Pharm. 2009 Feb;35(2):177-84. doi: 10.1080/03639040802235894.

Abstract

A novel poly(lactic acid-co-glycolic acid) nanoparticle loaded with insulin-lauryl sulfate complex was prepared by spontaneous emulsion solvent diffusion method. The effects of key parameters such as agitation speed, poly(vinyl alcohol) concentration, solvent composition, polymer concentration, and the volume of external aqueous phase on the properties of the nanoparticles were investigated. To enhance the drug recovery and drug content simultaneously, a response surface methodology with five-level, two-factor central composite design was employed. The weight ratio of polymer to drug and volume ratio of external aqueous phase to solvent phase were selected as controlled factors on account of their interactions found in the monofactorial investigations. The experimental datum allowed the development of quadratic models (p < .05) describing the inter-relationships between the dependent and independent variables. By solving the regression equation, and graphic analyzing the response surface contour and plots, the optimum values of the two factors were determined as 20/1 and 10/1. The optimized conditions led to 89.6% of drug recovery and 4.57% of drug content during nanoparticle preparation.

摘要

通过自发乳化溶剂扩散法制备了一种负载胰岛素 - 月桂醇硫酸酯复合物的新型聚乳酸 - 乙醇酸共聚物纳米颗粒。研究了搅拌速度、聚乙烯醇浓度、溶剂组成、聚合物浓度和外水相体积等关键参数对纳米颗粒性质的影响。为了同时提高药物回收率和药物含量,采用了五级、两因素中心复合设计的响应面法。鉴于在单因素研究中发现的聚合物与药物的重量比和外水相与溶剂相的体积比之间的相互作用,将它们选为控制因素。实验数据使得能够建立描述因变量和自变量之间相互关系的二次模型(p <.05)。通过求解回归方程,并对响应面轮廓和图进行图形分析,确定这两个因素的最佳值为20/1和10/1。优化条件使得纳米颗粒制备过程中的药物回收率达到89.6%,药物含量达到4.57%。

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