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Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL-PEG-PCL hydrogel. Part 2: sol-gel-sol transition and drug delivery behavior.

机译:基于热敏PCL-PEG-PCL水凝胶的可生物降解的原位凝胶形成控制药物递送系统。第2部分:溶胶-凝胶-溶胶转变和药物传递行为。

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摘要

In this work, a biodegradable and injectable in situ gel-forming controlled drug delivery system based on thermosensitive poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) hydrogel was studied. The prepared PCEC hydrogel undergoes temperature-dependent sol-gel-sol transition, which is a flowing sol at ambient temperature and turns into a non-flowing gel at around physiological body temperature. Furthermore, the sol-gel phase transition mechanism was investigated using (13)C-nuclear magnetic resonance imaging and a laser diffraction particle size analyzer. The in vitro release behaviors of several model drugs, including a hydrophilic small-molecule drug, a hydrophobic small-molecule drug and a macromolecular protein drug, from PCEC hydrogel were also investigated in detail. The results showed that the model drugs could be released from the PCEC hydrogel system over a sustained period. In addition, an anaesthesia assay was conducted using the tail flick latency (TFL) test to evaluate the in vivo controlled drug delivery effect of the PCEC hydrogel system. In the TFL assay, a lidocaine-loaded PCEC hydrogel produced significantly longer-lasting local anaesthetic effects compared with lidocaine aqueous solution at the same dose. Therefore, PCEC hydrogel is promising for use as an injectable local drug delivery system.
机译:在这项工作中,研究了一种基于热敏性聚(ε-己内酯)-聚(乙二醇)-聚(ε-己内酯)(PCEC)水凝胶的可生物降解和可注射的原位凝胶形成控制药物递送系统。制备的PCEC水凝胶经历与温度有关的溶胶-凝胶-溶胶转变,该转变在环境温度下为流动的溶胶,在生理温度左右时变为不流动的凝胶。此外,使用(13)C-核磁共振成像和激光衍射粒度分析仪研究了溶胶-凝胶相变机理。还详细研究了几种模型药物在体外从PCEC水凝胶中的释放行为,包括亲水性小分子药物,疏水性小分子药物和高分子蛋白药物。结果表明,模型药物可以在一段持续时间内从PCEC水凝胶系统中释放出来。此外,使用甩尾潜伏期(TFL)测试进行了麻醉分析,以评估PCEC水凝胶系统的体内控制药物递送效果。在TFL分析中,与相同剂量的利多卡因水溶液相比,负载利多卡因的PCEC水凝胶产生明显更持久的局部麻醉作用。因此,PCEC水凝胶有望用作可注射的局部药物输送系统。

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