PLGA implants: How Poloxamer/PEO addition slows down or accelerates polymer degradation and drug release
PLGA implants: How Poloxamer/PEO addition slows down or accelerates polymer degradation and drug release
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DOI：
10.1016/j.jconrel.2017.03.009
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发表时间：
2017-05-10
影响因子：
10.8
通讯作者：
Siepmann, J.
中科院分区：
文献类型：
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作者：
Yelles, M. C. Hamoudi-Ben;Tan, V. Tran;Siepmann, J.
本研究的目的是评价向载有丙胺卡因的PLGA基植入物中加入少量亲水性聚合物（泊洛沙姆188和PEO 200 kDa）的影响。特别强调了制备技术类型的重要性：研磨药物-聚合物粉末混合物的直接压缩与载药微粒的压缩（通过喷雾干燥制备）。在暴露于pH 7.4的磷酸盐缓冲液之前和之后，例如使用光学和扫描电子显微镜、X射线衍射、DSC和GPC对植入物进行彻底表征。有趣的是，根据制备方法的类型，将泊洛沙姆/PEO添加到PLGA植入物中对所得药物释放动力学具有相反的影响：在通过压缩研磨的药物-聚合物粉末共混物制备的植入物的情况下，药物释放加速，而当通过压缩载药的PLGA微粒制备植入物时，药物释放减慢。这些现象可以通过植入物暴露于释放介质时的溶胀/崩解行为来解释。由压缩微粒组成的系统保持完整，自催化效应非常重要。亲水性聚合物的存在促进水渗透到这些装置中，减缓PLGA降解和药物释放。相比之下，由压缩的药物-聚合物粉末混合物组成的植入物快速（至少部分）崩解，自催化作用不太重要。在这些情况下，加入亲水性聚合物促进酯键裂解，导致PLGA降解和药物释放加速。(C)2017爱思唯尔B. V.保留所有权利。
The aim of this study was to evaluate the impact of the addition of small amounts of hydrophilic polymers (Poloxamer 188 and PEO 200 kDa) to PLGA-based implants loaded with prilocaine. Special emphasis was placed on the importance of the type of preparation technique: direct compression of milled drug-polymer powder blends versus compression of drug loaded microparticles (prepared by spray-drying). The implants were thoroughly characterized before and upon exposure to phosphate buffer pH 7.4, e.g. using optical and scanning electron microscopy, X-ray diffraction, DSC and GPC. Interestingly, the addition of Poloxamer/PEO to the PLGA implants had opposite effects on the resulting drug release kinetics, depending on the type of preparation method: in the case of implants prepared by compression of milled drug-polymer powder blends, drug release was accelerated, whereas it was slowed down when the implants were prepared by compression of drug loaded PLGA microparticles. These phenomena could be explained by the swelling/disintegration behavior of the implants upon exposure to the release medium. Systems consisting of compressed microparticles remained intact and autocatalytic effects were of major importance. The presence of a hydrophilic polymer facilitated water penetration into these devices, slowing down PLGA degradation and drug release. In contrast, implants consisting of compressed drug-polymer powder blends rapidly (at least partially) disintegrated and autocatalysis was much less important. In these cases, the addition of a hydrophilic polymer facilitated ester bond cleavage, leading to accelerated PLGA degradation and drug release. (C) 2017 Elsevier B.V. All rights reserved.