Mukherjee Biswajit, Santra Kousik, Pattnaik Gurudutta, Ghosh Soma
Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India.
Int J Nanomedicine. 2008;3(4):487-96. doi: 10.2147/ijn.s3938.
Controlled drug delivery technology of proteins/peptides from biodegradable nanoparticles has emerged as one of the eminent areas to overcome formulation associated problems of the macromolecules. The purpose of the present investigation was to develop protein-loaded nanoparticles using biodegradable polymer poly L-lactide-co-glycolidic acid (PLGA) with bovine serum albumin (BSA) as a model protein. Despite many studies available with PLGA-based protein-loaded nanoparticles, production know-how, process parameters, protein loading, duration of protein release, narrowing polydispersity of particles have not been investigated enough to scale up manufacturing of protein-loaded nanoparticles in formulations. Different process parameters such as protein/polymer ratio, homogenizing speed during emulsifications, particle surface morphology and surface charges, particle size analysis and in-vitro protein release were investigated. The in-vitro protein release study suggests that release profile of BSA from nanoparticles could be modulated by changing protein-polymer ratios and/or by varying homogenizing speed during multiple-emulsion preparation technique. The formulation prepared with protein-polymer ratio of 1:60 at 17,500 rpm gave maximum protein-loading, minimum polydispersion with maximally sustained protein release pattern, among the prepared formulations. Decreased (10,000 rpm) or enhanced (24,000 rpm) homogenizing speeds resulted in increased polydispersion with larger particles having no better protein-loading and -release profiles in the present study.
基于可生物降解纳米颗粒的蛋白质/肽控释技术已成为克服大分子制剂相关问题的重要领域之一。本研究的目的是以牛血清白蛋白（BSA）作为模型蛋白，使用可生物降解聚合物聚丙交酯-乙交酯（PLGA）制备载蛋白纳米颗粒。尽管已有许多关于基于PLGA的载蛋白纳米颗粒的研究，但生产技术、工艺参数、蛋白载量、蛋白释放持续时间以及颗粒多分散性的缩小等方面尚未得到充分研究，不足以扩大制剂中载蛋白纳米颗粒的生产规模。研究了不同的工艺参数，如蛋白/聚合物比例、乳化过程中的均质速度、颗粒表面形态和表面电荷、粒径分析以及体外蛋白释放情况。体外蛋白释放研究表明，通过改变蛋白-聚合物比例和/或在复乳制备技术中改变均质速度，可以调节BSA从纳米颗粒中的释放曲线。在所制备的制剂中，以1:60的蛋白-聚合物比例在17,500转/分钟的条件下制备的制剂具有最大的蛋白载量、最小的多分散性以及最大程度的持续蛋白释放模式。在本研究中，降低（10,000转/分钟）或提高（24,000转/分钟）的均质速度会导致多分散性增加，颗粒变大，且蛋白载量和释放曲线并无改善。
