Product Development Cell, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
J Microencapsul. 2010;27(6):552-60. doi: 10.3109/02652048.2010.489974.
Controlled release formulation of recombinant human growth hormone (r-hGH) was achieved using poly lactide-co-glycolide (PLGA) polymer. Denaturation of r-hGH by dichloromethane during primary emulsification step of particle preparation was minimized by using human serum albumin whereas inclusion of sucrose and sodium bicarbonate helped in reducing protein denaturation during lyophilization and polymer particle degradation. Encapsulation efficiency of r-hGH entrapped in PLGA particles (size approximately 30 microm) was around 45% with protein load 20 microg of r-hGH/mg of polymer particles. Porous particles showed quick release of r-hGH in comparison to non-porous particles in vitro. More than 10 ng/mL of bioactive r-hGH was found in the serum of the experimental animals observed for a 30-day period after a single intramuscular injection of the polymeric formulation. Incorporation of optimal stabilizers is thus essential for the development of a stable, month long controlled release of polymer particle based r-hGH formulation.
采用聚丙交酯-乙交酯共聚物(PLGA)聚合物实现了重组人生长激素(r-hGH)的控释制剂。通过在颗粒制备的初级乳化步骤中使用人血清白蛋白,最大限度地减少了二氯甲烷对 r-hGH 的变性,而添加蔗糖和碳酸氢钠有助于减少冷冻干燥和聚合物颗粒降解过程中的蛋白质变性。包封在 PLGA 颗粒(大小约 30 微米)中的 r-hGH 的包封效率约为 45%,蛋白质负载为 20 微克 r-hGH/毫克聚合物颗粒。与非多孔颗粒相比,多孔颗粒在体外表现出 r-hGH 的快速释放。在单次肌肉内注射聚合物制剂后 30 天的观察期内,实验动物的血清中发现了超过 10 ng/mL 的生物活性 r-hGH。因此,对于开发稳定的、长达一个月的基于聚合物颗粒的 r-hGH 制剂的控释制剂,加入最佳稳定剂是必不可少的。