Ring inserts as a useful strategy to prepare tip-loaded microneedles for long-acting drug delivery with application in HIV pre-exposure prophylaxis
Ring inserts as a useful strategy to prepare tip-loaded microneedles for long-acting drug delivery with application in HIV pre-exposure prophylaxis
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DOI：
10.1016/j.matdes.2022.111416
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发表时间：
2022-11-24
影响因子：
8.4
通讯作者：
Donnelly, Ryan F.
中科院分区：
文献类型：
--
作者：
Paredes, Alejandro J.;Permana, Andi Dian;Donnelly, Ryan F.
过去十年，微针阵列贴片（MAP）的作用，特别是溶解 MAP 在透皮给药中的作用呈指数级增长。 MAP 能够在活性皮肤中形成药物库，难溶性药物可在其中以长效方式溶解，这在治疗多种疾病方面显示出前景。这些系统的制造可能会带来一些挑战，包括基板中存在气泡以及由此导致的微针形成和药物含量缺乏均匀性。在这里，我们提出了一种基于环插入物的简单方法，使用抗逆转录病毒药物卡博特韦钠 (CAB) 生产尖端装载的 MAP。根据所进行的机械表征，获得的 MAP 在微针形成方面表现出高度均匀性，并且具有合适的插入能力。基于实验设计的优化表明，离心参数对使用 Franz 细胞切除的新生猪皮肤中 MAP 的皮肤沉积有显着影响，其值范围为 62.24 +/- 47.13 lg 到 174.13 +/- 41.10 lg CAB。在大鼠中进行的药代动力学研究证明，MAP 能够将 CAB 治疗血浆水平维持 14 天，Tmax 值在 5 至 8 天之间达到。(c) 2022 作者。由 Elsevier Ltd 出版。这是一篇基于 CC BY 许可证 (http://creativecommons.org/licenses/by/4.0/) 的开放获取文章。
The role of microneedle array patches (MAPs) and, in particular, dissolving MAPs in transdermal drug delivery has increased exponentially over the last decade. MAPs are able to form drug depots in the viable skin from where poorly soluble drugs dissolve in a long-acting fashion, showing promise in the management of multiple diseases. The manufacture of these systems can present some challenges, including the presence of bubbles in the baseplates and consequent lack of uniformity in microneedle formation and drug content. Here, we present a simple method based on ring inserts to produce tip-loaded MAPs using the antiretroviral drug cabotegravir sodium (CAB). The obtained MAPs presented a high uniformity in terms of microneedle formation, and a suitable insertion capability, as per the mechanical characterisation performed. An optimisation based on design of experiments revealed that centrifugation parameters had a significant impact on the skin deposition of the MAPs in excised neonatal porcine skin using Franz cells, with values ranging from 62.24 +/- 47.13 lg to 174.13 +/- 41.10 lg of CAB. Pharmacokinetic studies carried out in rats evidenced the capacity of the MAPs to maintain therapeutic plasma levels of CAB for 14 days, with Tmax values reached between 5 and 8 days.(c) 2022 The Author(s). Published by Elsevier Ltd.This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).