Microencapsulation of amorphous solid dispersions of fenretinide enhances drug solubility and release from PLGA in vitro and in vivo.
Microencapsulation of amorphous solid dispersions of fenretinide enhances drug solubility and release from PLGA in vitro and in vivo.
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DOI：
10.1016/j.ijpharm.2020.119475
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发表时间：
2020-08-30
影响因子：
5.8
通讯作者：
Schwendeman SP
中科院分区：
文献类型：
--
作者：
Nieto K;Mallery SR;Schwendeman SP
本研究的目的是开发芬维A胺（4HPR）的固体分散体，将其掺入聚乳酸-乙醇酸共聚物（PLGA）毫圆柱形植入物中，并在体外和体内评估所得植入物，以用于口腔癌化学预防的未来应用。由于4HPR的极端疏水性，制备了4HPR-聚乙烯吡咯烷酮（PVP）无定形固体分散体（ASD）以增强溶解度。最佳 PVP-4HPR 比例为 9/1 (w/w)，在水介质中的溶解度提高了 50 倍，并持续超过 1 周。将 PVP-4HPR ASD 颗粒装入 PLGA 毫缸中，并在 PBST 中体外评估药物释放，并通过大鼠皮下注射恢复来评估体内药物释放。虽然 PLGA PVP-4HPR 毫圆柱的初始配方在 28 天后体外仅释放 10% 4HPR，但在 PVP-4HPR ASD 中添加增塑剂邻乙酰基柠檬酸三乙酯 (TEAC) 后，药物释放总量增加了 5.6 倍。值得注意的是，TEAC-PVP-4HPR PLGA 植入物在体内 1 个月内表现出缓慢、连续且几乎完全的释放，而我们之前报道的含有增溶剂和成孔剂的配方的释放率为 25%。因此，PLGA增塑剂和ASD形成的组合为特别难以配制的药物4HPR提供了体内长期控释的途径，并为口腔癌啮齿动物模型的未来评估提供了合适的配方。
The purpose of this study was to develop solid dispersions of fenretinide(4HPR), incorporate them into poly (lactic-co-glycolic)(PLGA) millicylindrical implants, and evaluate the resulting implants in vitro and in vivo for future applications in oral cancer chemoprevention. Due to the extreme hydrophobicity of 4HPR, 4HPR-polyvinylpyrrolidone (PVP) amorphous solid dispersions(ASDs) were prepared for solubility enhancement. The optimal PVP-4HPR ratio of 9/1 (w/w) provided a 50-fold solubility enhancement in aqueous media, which was sustained over 1 week. PVP-4HPR ASD particles were loaded into PLGA millicylinders and drug release was evaluated in vitro in PBST and in vivo by recovery from subcutaneous injection in rats. While initial formulations of PLGA PVP-4HPR millicylinders only released 10% 4HPR in vitro after 28 days, addition of the plasticizer triethyl-o-acetyl-citrate(TEAC) into PVP-4HPR ASDs resulted in a 5.6-fold total increase in drug release. Remarkably, the TEAC-PVP-4HPR PLGA implants demonstrated slow, continuous, and nearly complete release over 1 month in vivo compared to a 25% release for our previously reported formulation incorporating solubilizers and pore-forming agents. Hence, a combination of PLGA plasticizer and ASD formation provides an avenue for long-term controlled release in vivo for the exceptionally difficult drug to formulate, 4HPR, and a suitable formulation for future evaluation in rodent models of oral cancer.
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影响因子：
3.7
作者：
Desai, Kashappa-Goud H.;Mallery, Susan R.;Holpuch, Andrew S.;Schwendeman, Steven P.
通讯作者：
Schwendeman, Steven P.
影响因子：
--
作者：
Holpuch AS;Desai KG;Schwendeman SP;Mallery SR
通讯作者：
Mallery SR
影响因子：
3.8
作者：
Sun, Ye;Tao, Jing;Yu, Lian
通讯作者：
Yu, Lian
影响因子：
7.3
作者：
Illingworth NA;Boddy AV;Daly AK;Veal GJ
通讯作者：
Veal GJ
影响因子：
6
作者：
Orienti, I.;Zuccari, G.;Montaldo, P. G.
通讯作者：
Montaldo, P. G.