Carrasquillo K G, Carro J C, Alejandro A, Toro D D, Griebenow K
Department of Chemistry, University of Puerto Rico, San Juan 00931-3346, USA.
J Pharm Pharmacol. 2001 Jan;53(1):115-20. doi: 10.1211/0022357011775091.
Protein stability is a factor limiting the use of sustained-release devices in medical applications. The aim of this study was to reduce structural perturbations occurring in the frequently used model protein, bovine serum albumin (BSA), upon microencapsulation in poly(D,L-lactide-co-glycolide) (PLG) microspheres. Spray freeze-dried BSA was encapsulated into PLG microspheres by a completely non-aqueous oil-in-oil encapsulation procedure. FTIR spectroscopy was used as a non-invasive method to quantify procedure-induced structural perturbations in BSA. Spray-freeze drying of BSA caused significant structural perturbations that were minimized by co-spray freeze-drying BSA with trehalose. BSA-containing microspheres were produced by suspension of the powder by homogenization in methylene chloride containing PLG, followed by formation of coacervate droplets by the addition of silicon oil and hardening using the solvent heptane. Resulting microspheres had dimensions of approximately 100 microm and the encapsulation efficiency for BSA was > 90%. FTIR data showed that the structure of the BSA-trehalose formulation encapsulated into PLG microspheres was less perturbed than that of BSA obtained from buffer alone. The results demonstrate that the structure-guided encapsulation approach introduced for non-aqueous casting encapsulation procedures can be extended to the non-aqueous production of pharmaceutically relevant PLG microspheres involving a complex encapsulation procedure.
蛋白质稳定性是限制缓释装置在医学应用中使用的一个因素。本研究的目的是减少常用模型蛋白牛血清白蛋白（BSA）在聚（D，L-丙交酯-乙交酯）（PLG）微球中微囊化时发生的结构扰动。通过完全非水的油包油包封程序将喷雾冷冻干燥的BSA包封到PLG微球中。傅里叶变换红外光谱（FTIR）被用作一种非侵入性方法来量化程序诱导的BSA结构扰动。BSA的喷雾冷冻干燥引起了显著的结构扰动，通过将BSA与海藻糖共喷雾冷冻干燥可将其最小化。含BSA的微球是通过在含有PLG的二氯甲烷中均质化悬浮粉末，然后加入硅油形成凝聚液滴并使用溶剂庚烷硬化来制备的。所得微球的尺寸约为100微米，BSA的包封效率>90%。FTIR数据表明，包封到PLG微球中的BSA-海藻糖制剂的结构扰动比仅从缓冲液中获得的BSA的结构扰动小。结果表明，为非水浇铸包封程序引入的结构导向包封方法可以扩展到涉及复杂包封程序的药学相关PLG微球的非水生产中。
