PEG modulated release of etanidazole from implantable PLGA/PDLA discs.
PEG modulated release of etanidazole from implantable PLGA/PDLA discs.
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PEG 调节依他硝唑从植入式 PLGA/PDLA 圆盘中的释放。
DOI：
10.1016/s0142-9612(02)00034-0
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发表时间：
2002
期刊：
影响因子：
14
通讯作者：
Chi‐Hwa Wang
中科院分区：
文献类型：
--
作者：
Fangjing Wang;Timothy C. P. Lee;Chi‐Hwa Wang
在这项工作中，依他硝唑（一种类型的低氧放射增敏剂）封装到喷雾干燥的聚（d，l-丙交酯-共-乙交酯）（PLGA）微球，然后压缩成控制释放应用光盘。依他硝唑的特点是细胞内谷胱甘肽耗竭和谷胱甘肽转移酶抑制，从而提高对辐射的敏感性。它对肿瘤细胞也具有细胞毒性，并可通过激活其肿瘤细胞杀伤能力使一些烷化剂化学增敏。考察了不同制备条件下依他硝唑微球和圆片的释药特性。考察了微球的释放特性、形态变化、粒径大小和包封率。由于比表面积的减小，依他硝唑在直径13 mm、厚度1 mm的压片中的释放速率远低于微球。在第一天1%释放的初始突释之后，第一周内的累积释放小于2%，直到一个月后发生二次突释（由聚合物降解引起）。一些关键的制备条件，如载药量、圆盘厚度和直径以及压片压力，可以影响依他硝唑从圆盘的初始突释。然而，它们都不能显著地使释放更均匀。相比之下，聚乙二醇（PEG）的掺入可以大大提高光盘的释放速率，也减少了二次突释效应，从而实现约2个月的持续释放。
In this work, etanidazole (one type of hypoxic radiosensitizer) is encapsulated into spray dried poly(d,l-lactide-co-glycolide) (PLGA) microspheres and then compressed into discs for controlled release applications. Etanidazole is characterized by intracellular glutathione depletion and glutathione transferases inhibition, thereby enhancing sensitivity to radiation. It is also cytotoxic to tumor cells and can chemosensitize some alkylating agents by activating their tumor cell killing capabilities. We observed the release characteristics of etanidazole in the dosage forms of microspheres and discs, subjected to different preparation conditions. The release characteristics, morphology changes, particle size, and encapsulation efficiency of microspheres are also investigated. The release rate of etanidazole from implantable discs (13mm in diameter, 1mm in thickness, fabricated by a press) is much lower than microspheres due to the reduced specific surface. After the initial burst of 1% release for the first day, the cumulative release within the first week is less than 2% until a secondary burst of release (caused by polymer degradation) occurs after one month. Some key preparation conditions such as drug loadings, disc thickness and diameter, and compression pressure can affect the initial burst of etanidazole from the discs. However, none of them can significantly make the release more uniform. In contrast, the incorporation of polyethylene glycol (PEG) can greatly enhance the release rate of discs and also reduces the secondary burst effect, thereby achieving a sustained release for about 2 months.
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DOI：
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