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Mechanism of drug release from double-walled PDLLA(PLGA) microspheres

机译：双壁PDLLA（PLGA）微球的药物释放机制

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摘要

The drug release and degradation behavior of two double-walled microsphere formulations consisting of a doxorubicin loaded poly(D,L-lactic-co-glycolic acid) (PLGA) core (~46 kDa) surrounded by a poly(D,L-lactic acid) (PDLLA) shell layer (~55 and 116 kDa) were examined. It was postulated that different molecular weights of the shell layer could modulate the erosion of the outer coating and limit the occurrence of water penetration into the inner drug-loaded core on various time scales, and therefore control the drug release from the microspheres. For both microsphere formulations, the drug release profiles were observed to be similar. The degradation of the microspheres was monitored for a period of about nine weeks and analyzed using scanning electron microscopy, laser scanning confocal microscopy, and gel permeation chromatography. Interestingly, both microsphere formulations exhibited occurrence of bulk erosion of PDLLA on a similar time scale despite different PDLLA molecular weights forming the shell layer. The shell layer of the double-walled microspheres served as an effective diffusion barrier during the initial lag phase period and controlled the release rate of the hydrophilic drug independent of the molecular weight of the shell layer.
机译：由载有阿霉素的聚（D，L-乳酸-乙醇酸共聚物）（PLGA）核心（〜46 kDa）组成的两个双壁微球制剂的药物释放和降解行为（PDLLA）壳层（〜55和116 kDa）进行了检测。据推测，壳层的不同分子量可以调节外涂层的侵蚀，并在不同的时间尺度上限制水渗透到内载药物的核心中，从而控制药物从微球的释放。对于两种微球制剂，观察到药物释放曲线相似。监测微球的降解约九周，并使用扫描电子显微镜，激光扫描共聚焦显微镜和凝胶渗透色谱法进行分析。有趣的是，尽管形成壳层的PDLLA分子量不同，但两种微球制剂都在相似的时间尺度上显示出PDLLA的整体腐蚀。双壁微球的壳层在初始滞后阶段期间充当有效的扩散屏障，并控制亲水性药物的释放速率，而与壳层的分子量无关。

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