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聚合物共混对 HIV 暴露前预防(PrEP)皮下可生物降解植入物性能的影响。

Effects of Polymer Blending on the Performance of a Subcutaneous Biodegradable Implant for HIV Pre-Exposure Prophylaxis (PrEP).

机构信息

Engineered Systems RTI International, Durham, NC 27709, USA.

Center for AIDS Prevention Studies, Department of Medicine, University of California San Francisco, San Francisco, CA 94104, USA.

出版信息

Int J Mol Sci. 2021 Jun 18;22(12):6529. doi: 10.3390/ijms22126529.

Abstract

Long-acting (LA) HIV pre-exposure prophylaxis (PrEP) can mitigate challenges of adhering to daily or on-demand regimens of antiretrovirals (ARVs). We are developing a subcutaneous implant comprising polycaprolactone (PCL) for sustained delivery of ARVs for PrEP. Here we use tenofovir alafenamide (TAF) as a model drug. Previously, we demonstrated that the release rates of drugs are controlled by the implant surface area and wall thickness, and the molecular weight (MW) of PCL. Here, we further advance the implant design and tailor the release rates of TAF and the mechanical integrity of the implant through unique polymer blend formulations. In vitro release of TAF from the implant exhibited zero-order release kinetics for ~120 days. TAF release rates were readily controlled via the MW of the polymer blend, with PCL formulations of higher MW releasing the drug faster than implants with lower MW PCL. Use of polymer MW to tune drug release rates is partly explained by PCL crystallinity, as higher PCL crystalline material is often associated with a slower release rate. Moreover, results showed the ability to tailor mechanical properties via PCL blends. Blending PCL offers an effective approach for tuning the ARV release rates, implant duration, and integrity, and ultimately the biodegradation profiles of the implant.

摘要

长效(LA)HIV 暴露前预防(PrEP)可以缓解每日或按需服用抗逆转录病毒药物(ARV)的困难。我们正在开发一种包含聚己内酯(PCL)的皮下植入物,用于持续输送 ARV 进行 PrEP。在这里,我们使用替诺福韦艾拉酚胺(TAF)作为模型药物。此前,我们证明了药物的释放速率受植入物表面积和壁厚以及 PCL 分子量(MW)的控制。在这里,我们通过独特的聚合物共混配方进一步推进了植入物设计,并调整了 TAF 的释放速率和植入物的机械完整性。TAF 从植入物中的体外释放表现出约 120 天的零级释放动力学。通过聚合物共混物的 MW 可以很容易地控制 TAF 的释放速率,MW 较高的 PCL 配方比 MW 较低的 PCL 植入物更快地释放药物。使用聚合物 MW 来调节药物释放速率部分归因于 PCL 的结晶度,因为较高的 PCL 结晶材料通常与较慢的释放速率相关。此外,结果表明通过 PCL 共混物可以调整机械性能。PCL 共混提供了一种有效的方法来调节 ARV 释放速率、植入物持续时间和完整性,以及最终调节植入物的生物降解特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/8235439/44f28911261f/ijms-22-06529-g001.jpg

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