Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden.
Int J Pharm. 2011 May 16;409(1-2):194-202. doi: 10.1016/j.ijpharm.2011.02.066. Epub 2011 Mar 8.
Poly(D,L-lactide-co-glycolide) (PLG) is the most frequently used biodegradable polymer in the controlled release of an encapsulated drug. The purpose of this work was to explain the surprisingly slow diffusion through this polymer, and locate the major source of mass transport resistance. Diffusion of human growth hormone (hGH) and glucose through PLG films was undetectable (using a diffusion cell), although the degraded polymer contained several times more water than polymer mass. In vitro release of hGH from PLG-coated particles also showed a surprisingly slow rate of release. Non-porous regions inside the PLG films were detected after three weeks of degradation using dextran-coupled fluorescent probes and confocal microscopy. The findings were supported by scanning electron microscopy. Diffusion through PLG films degraded for five weeks was significantly increased when the porosity of both surfaces was increased due to the presence of ZnCl(2) in the buffer the last 3 days of the degradation period. The results indicated high mass transport resistance inside the films after three weeks of degradation, and at the surfaces after five weeks of degradation. These results should also be applicable to microparticles of different sizes. Knowledge of the reason for transport resistance is important in the development of pharmaceuticals and when modifying the rate of drug release.
聚（D，L-丙交酯-co-乙交酯）（PLG）是在包封药物的控制释放中最常使用的可生物降解聚合物。本工作的目的是解释通过这种聚合物的扩散速度为何出人意料地慢，并找出主要的传质阻力源。尽管降解后的聚合物所含的水量比聚合物的质量多几倍，但人生长激素（hGH）和葡萄糖通过 PLG 膜的扩散是无法检测到的（使用扩散池）。PLG 包衣颗粒中 hGH 的体外释放也显示出出人意料的缓慢释放速率。使用葡聚糖偶联荧光探针和共焦显微镜在降解三周后检测到 PLG 膜内的非多孔区域。扫描电子显微镜的结果也支持这一发现。降解五周后的 PLG 膜的扩散在最后 3 天降解缓冲液中存在 ZnCl2 时，由于两面的多孔性增加而显著增加。结果表明，降解三周后膜内的传质阻力很大，降解五周后在膜表面的传质阻力也很大。这些结果也应该适用于不同大小的微球。了解传质阻力的原因对于药物的开发和药物释放速率的调节非常重要。
