mPEG-PLA microspheres with narrow size distribution increase the controlled release effect of recombinant human growth hormone
mPEG-PLA microspheres with narrow size distribution increase the controlled release effect of recombinant human growth hormone
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窄粒径分布的mPEG-PLA微球提高重组人生长激素的控释效果
DOI：
10.1039/c1jm12643a
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发表时间：
2011-01-01
影响因子：
--
通讯作者：
Ma, Guang-Hui
中科院分区：
文献类型：
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作者：
Wei, Yi;Wang, Yu-Xia;Ma, Guang-Hui
本研究的总体目标是制备具有窄尺寸分布的两亲性聚单甲氧基聚乙二醇-D,L-丙交酯（mPEG-PLA、PELA）微球，用于在不使用任何外源稳定赋形剂的情况下持续释放重组人生长激素（rhGH）。为了获得窄粒径分布的微球，我们采用了双乳化法结合预混膜乳化技术。对PELA微球的形态、内部结构、rhGH包封率、体外释放和rhGH稳定性进行了详细表征。将结果与包封在聚(D,L-乳酸)(PLA)和聚(D,L-乳酸-乙醇酸)(PLGA)微球中的rhGH的结果进行比较。所有微球均具有较窄的尺寸分布，平均直径为 2 μm。 PELA、PLA和PLGA微球的包封率分别为89.3%、65.0%和58.6%。 PELA 微球最初爆发释放 14.2% rhGH，随后在 45 天内持续释放 78.3%。而 PLA 和 PLGA 微球的突释水平较高，分别为 22.3% 和 26.2%，随后的释放水平分别为 49.1% 和 60.5%。此外，PELA 微球比 PLA 和 PLGA 微球保持了更好的 rhGH 完整性。这些结果表明 PELA 是一种用于封装 rhGH 的优异聚合物。我们认为，mPEG-PLA 嵌段共聚物的作用方式与表面活性剂类似，并且它可以在双相界面上自我定向，从而最大限度地减少蛋白质与油/水界面的接触，从而实现蛋白质稳定。此外，使用共焦激光扫描显微镜阐明了rhGH封装和rhGH稳定性的微观机制。这些结果对于使用 PELA 微球构建 rhGH 缓释系统具有广阔的前景。
The overall goal of this research is to prepare amphiphilic poly(monomethoxypolyethylene glycol-co-D,L-lactide) (mPEG-PLA, PELA) microspheres with narrow size distribution for sustained release of recombinant human growth hormone (rhGH) without any exogenous stabilizing excipients. In order to obtain microspheres with narrow size distribution, we used a double emulsion method combined with a premix membrane emulsification technique. The morphology, internal structure, rhGH encapsulation efficiency, in vitro release and rhGH stability of PELA microspheres were characterized in detail. The results were compared with those of rhGH encapsulated in poly(D,L-lactic acid) (PLA) and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres. All microspheres possessed a narrow size distribution and had mean diameters of 2 μm. The encapsulation efficiency of PELA, PLA, and PLGA microspheres were 89.3%, 65.0% and 58.6%, respectively. PELA microspheres showed an initial burst release of 14.2% rhGH, followed by a constant release of 78.3% over a 45-day period. Whereas, the PLA and PLGA microspheres showed higher burst levels of 22.3% and 26.2%, followed by release of 49.1% and 60.5%, respectively. In addition, the PELA microspheres maintained much better integrity of rhGH than PLA and PLGA microspheres. These results suggested that PELA is an excellent polymer for encapsulating rhGH. We propose that the mPEG-PLA block copolymer acts in a similar way to a surfactant and that it may orientate itself on the biphasic interface, thereby minimizing the contact of protein with the oil/water interface for protein stabilization. Furthermore, the microcosmic mechanisms responsible for rhGH encapsulation and rhGH stability were elucidated using a confocal laser scanning microscope. These results are promising for the construction of a sustained release system for rhGH using PELA microspheres.