Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang, China.
Int J Nanomedicine. 2009;4:321-33. doi: 10.2147/ijn.s8501. Epub 2009 Dec 29.
Response surface methodology (RSM) was used to optimize the process of preparing bovine serum albumin (BSA) nanoparticles by desolvation, then the resulting BSA nanoparticles (BSANPs) were conjugated with folate to produce a drug carrier system that can specifically target tumors. The anticancer drug, vinblastine sulfate (VBLS), was loaded to this tumor-specific drug carrier system for the purpose of overcoming the nonspecific targeting characteristics and side effects of the drug. A central composite design was applied for modeling the process, which was composed of four independent variables, namely BSA concentration, the rate of adding ethanol (ethanol rate), ethanol amount, and the degree of crosslinking. The mean particle size and residual amino groups of the BSANPs were chosen as response variables. The interactive effects of the four independent variables on the response variables were studied. The characteristics of the nanoparticles; such as amount of folate conjugation, drug entrapment efficiency, drug-loading efficiency, surface morphology and release kinetics in vitro were investigated. Optimum conditions for preparing desired BSANPs, with a mean particle size of 156.6 nm and residual amino groups of 668.973 nM/mg, were obtained. The resulting folate-conjugated BSANPs (FA-BSANPs) showed a drug entrapment efficiency of 84.83% and drug-loading efficiency of 42.37%, respectively, and the amount of folate conjugation was 383.996 microM/g BSANPs. The results of this study indicate that using FA-BSANPs as a drug carrier system could be effective in targeting VBLS-sensitive tumors in the future.
响应面法（RSM）用于优化牛血清白蛋白（BSA）纳米颗粒的脱水制备工艺，然后将所得的 BSA 纳米颗粒（BSANPs）与叶酸缀合，以产生一种可以特异性靶向肿瘤的药物载体系统。将抗癌药物硫酸长春碱（VBLS）载入这种肿瘤特异性药物载体系统，以克服药物的非特异性靶向特性和副作用。采用中心复合设计对该过程进行建模，该设计由四个独立变量组成，即 BSA 浓度、乙醇添加速率（乙醇速率）、乙醇量和交联度。BSANPs 的平均粒径和残留氨基基团被选为响应变量。研究了四个独立变量对响应变量的相互作用影响。研究了纳米颗粒的特性；如叶酸缀合的量、药物包封效率、药物载药效率、表面形态和体外释放动力学。获得了制备理想 BSANPs 的最佳条件，平均粒径为 156.6nm，残留氨基基团为 668.973nM/mg。所得叶酸缀合的 BSANPs（FA-BSANPs）的药物包封效率为 84.83%，药物载药效率为 42.37%，BSANPs 的叶酸缀合量为 383.996μM/g。这项研究的结果表明，未来使用 FA-BSANPs 作为药物载体系统可能对靶向 VBLS 敏感的肿瘤有效。
