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首页> 外文期刊>Acta biomaterialia >Adjustable degradation and drug release of a thermosensitive hydrogel based on a pendant cyclic ether modified poly(ε-caprolactone) and poly(ethylene glycol)co-polymer.
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Adjustable degradation and drug release of a thermosensitive hydrogel based on a pendant cyclic ether modified poly(ε-caprolactone) and poly(ethylene glycol)co-polymer.

机译：基于环醚侧基修饰的聚（ε-己内酯）和聚（乙二醇）共聚物的热敏水凝胶的可调节降解和药物释放。

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摘要

The convenient and precise fabrication of drug-hydrogel formulations with satisfactory degradability and a well-controlled drug release profile are crucial factors for injectable hydrogel formulations in clinical applications. Here a new injectable thermosensitive hydrogel formed from poly(ε-caprolactone) (PCL)-poly(ethylene glycol)-poly(ε-caprolactone) amphiphilicco-polymers with 1,4,8-trioxa[4.6]spiro-9-undecanone (TOSUO) moieties incorporated in the poly(ε-caprolactone) (PCL)block (PECT) was constructed to provide a route to tailor the degradation and drug release behavior. The effect of hydrophilic cyclic ether moieties on the degradation of and drug release by PECT hydrogels were evaluated in vitro and in vivo. The results indicated that a freeze-dried powder of paclitaxel-loaded PECT nanoparticles rapidly dissolved in water at ambient temperature with slightly shaking and formed a stable injectable in situ drug-hydrogel formulation at body temperature, which is convenient for clinical operations because it avoids the need for pre-quenching or long-term incubation. The paclitaxel distribution was also more quantitative and homogeneous on entrapping paclitaxel in PECT nanoparticles. Further, the small number of pendant cyclic ether groups in PCL could decrease the cystallinity and hydrophobicity and, as a result, the in vitro and in vivo retention time of PECT hydrogels and the release of entrapped paclitaxel could be tuned from a few weeks to months by varying the amount of PTOSUO in the hydrophobic block. Significantly, paclitaxel-loaded PECT nanoparticles and free paclitaxel could be simultaneously released during the in vitro paclitaxel release from PECT hydrogels. A histopathological evaluation indicated that in vivo injected PECT hydrogels produced only a modest inflammatory response. Thus pendant cyclic ether modification of PCL could be an effective way to achieve the desired degradation and drug release profiles of amphiphilicco-polymer thermosensitive hydrogels and PECT hydrogels may be suitable for local drug delivery.
机译：具有令人满意的可降解性和良好控制的药物释放曲线的药物-水凝胶制剂的方便，精确的制备是临床应用中可注射水凝胶制剂的关键因素。在这里，一种新的可注射的热敏水凝胶由聚（ε-己内酯）（PCL）-聚（乙二醇）-聚（ε-己内酯）两亲聚合物与1,4,8-三氧杂[4.6] spiro-9-十一烷酮（构建并入聚（ε-己内酯）（PCL）嵌段（PECT）的TOSUO）部分，以提供定制降解和药物释放行为的途径。在体外和体内评估了亲水性环状醚部分对PECT水凝胶降解和药物释放的影响。结果表明，载有紫杉醇的PECT纳米颗粒的冻干粉末在室温下轻微摇动即可迅速溶于水，并在体温下形成稳定的可注射原位药物-水凝胶制剂，因为避免了这种操作，因此便于临床操作需要进行预淬灭或长期孵育。将紫杉醇截留在PECT纳米颗粒中时，紫杉醇的分布也更加定量和均一。此外，PCL中少量的环醚侧基可能会降低胱氨酸度和疏水性，因此，PECT水凝胶的体外和体内保留时间以及所捕获的紫杉醇的释放可以从几周到几个月不等。通过改变疏水性嵌段中PTOSUO的量。重要的是，在体外从PECT水凝胶中释放紫杉醇的过程中，可以同时释放载有紫杉醇的PECT纳米颗粒和游离紫杉醇。组织病理学评估表明，体内注射的PECT水凝胶仅产生适度的炎症反应。因此，PCL的环醚侧挂修饰可能是实现所需降解的有效方法，两亲聚合物热敏水凝胶和PECT水凝胶的药物释放曲线可能适合局部药物输送。

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