Schoubben Aurélie, Blasi Paolo, Giovagnoli Stefano, Perioli Luana, Rossi Carlo, Ricci Maurizio
Department of Chemistry and Technology of Drugs, School of Pharmacy, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy.
Eur J Pharm Sci. 2009 Feb 15;36(2-3):226-34. doi: 10.1016/j.ejps.2008.09.008. Epub 2008 Oct 2.
The aim of this work was to develop a novel composite alginate/poly(lactic-co-glycolic) acid microparticulate system for protein stabilization and delivery using bovine insulin as model drug. Alginate particles, prepared by ionic gelation, were embedded into PLGA microparticles using the solvent diffusion evaporation technique. Actual loading was determined by micro-BCA protein assay for total insulin and by reversed phase-high performance liquid chromatography for soluble insulin. Insulin loaded composite microparticles showed reproducible encapsulation efficiency with a higher soluble insulin content when compared to conventional microparticles. Bovine insulin in vitro release studies and adsorption behavior were investigated in 10 mM glycine buffer (pH 2.8) at 37 degrees C. The stability of bovine insulin, solubilized in the above mentioned buffer, was studied as well. In this case, bovine insulin showed to be instable at the investigated conditions and 55% of insulin was lost after 7 days. However, composite microparticle release, characterized by a low burst effect, lasted up to 4 months. Moreover, no significant peptide adsorption on blank PLGA or blank composite microparticles was observed while, a strong interaction between alginate particles and bovine insulin was detected.
这项工作的目的是开发一种新型的藻酸盐/聚（乳酸-共-乙醇酸）酸微颗粒系统，以牛胰岛素为模型药物用于蛋白质的稳定和递送。通过离子凝胶法制备的藻酸盐颗粒，采用溶剂扩散蒸发技术嵌入到聚乳酸-乙醇酸共聚物（PLGA）微颗粒中。通过微量BCA蛋白分析法测定总胰岛素含量，通过反相高效液相色谱法测定可溶性胰岛素含量来确定实际载药量。与传统微颗粒相比，载胰岛素复合微颗粒显示出可重复的包封效率，且可溶性胰岛素含量更高。在37℃下，于10 mM甘氨酸缓冲液（pH 2.8）中研究了牛胰岛素的体外释放研究和吸附行为。还研究了溶解在上述缓冲液中的牛胰岛素的稳定性。在这种情况下，牛胰岛素在所研究的条件下显示出不稳定，7天后55%的胰岛素损失。然而，复合微颗粒的释放具有低突释效应的特点，持续长达4个月。此外，在空白PLGA或空白复合微颗粒上未观察到明显的肽吸附，而检测到藻酸盐颗粒与牛胰岛素之间有强烈的相互作用。
