微球/温敏凝胶复合植入给药系统的释药特征及模型

Characterizing the drug release from the hydrogel drug delivery system incorporated with biodegradable microspheres

将载药微球分散在温敏凝胶中构成的复合埋植给药系统,可实现长期稳定给药。以载有纳曲酮的乳酸-乙醇酸共聚物(PLGA)微球与甲基纤维素温敏凝胶构成的释药系统为例,研究了药物在该系统中的释放动力学特征和模型。结果表明复合系统中的释药主要受药物在微球中的释放控制;水凝胶改变了微球的存在环境,增加了水的扩散阻力,使药物扩散系数减小,微球溶蚀速率降低,达到最大溶蚀速率的时间推迟,从而使释药速率降低并更加平稳。将上述影响引入微球释药模型,建立了微球-凝胶系统释药模型,模拟结果和实验数据吻合较好。通过调整微球材料的相对分子量和亲疏水性,实现了纳曲酮超过60 d的恒速释放。

The injectable gelling drug delivery system incorporated with biodegradable microspheres has great potential in implanted drug delivery for long-term controlled drug release. We investigated drug release in vitro in a model system which was composed by naltrexone-loaded PLGA microspheres and thermosensitive hydrogel consisted of methylcellulose, polyethylene glycol, sodium citrate and sodium alginate. In the microspheres-hydrogel composite system, drug release was dominated by drug diffusion in microspheres. The hydrogel affected the porosity, erosion and degradation of the microspheres, which resulted in the smaller drug diffusion coefficient, lower erosion rate and prolonged period to reach the maximal erosion rate. Therefore, it reduced and stabilized the drug release rate. These impacts of hydrogel were presented in the drug release model based on drug release from biodegradable polymeric micmspheres, and the developed model was well consistent with the experiment. The microspheres-hydrogel composite system realized the over 60-day steady release of naltrexone by opfLrnizing the molecular weight and hyhydrophilicity of PLGA.