Biocompatible Ionic Liquid-Mediated Micelles for Enhanced Transdermal Delivery of Paclitaxel
Biocompatible Ionic Liquid-Mediated Micelles for Enhanced Transdermal Delivery of Paclitaxel
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DOI：
10.1021/acsami.1c03111
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发表时间：
2021-04-23
影响因子：
9.5
通讯作者：
Goto, Masahiro
中科院分区：
文献类型：
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作者：
Ali, Md Korban;Moshikur, Rahman Md;Goto, Masahiro
化学药物细胞毒性剂如紫杉醇（PTX）被认为是治疗各种癌症所必需的。然而，PTX注射与严重的全身性副作用和高比例的患者不依从性相关。胶束制剂（MFs）是纳米药物递送系统，其为这些问题提供了解决方案。本文中，我们报道了一种用于PTX经皮递送的有利载体，其包含由两种生物相容性表面活性剂组成的新MF：油酸胆碱（[Cho][Ole]），其是表面活性离子液体（SAIL），和脱水山梨糖醇单月桂酸酯（Span-20）。溶解度评估证实，PTX通过PTX和SAIL[Cho][Ole]之间的多点氢键和阳离子-p和p-p相互作用容易溶解在基于SAIL的胶束中。动态光散射（DLS）和透射电子显微镜显示，在PTX的存在下，MF形成球形PTX负载胶束，在8.7-25.3 nm范围内均匀分布。根据DLS，胶束液滴的尺寸和尺寸分布在整个储存期间没有显著变化，证明其物理稳定性。使用Franz扩散池进行的体外透皮评估显示，MF吸收PTX的有效性是基于吐温80的制剂的4倍，是基于乙醇的制剂的6倍。体外和体内皮肤刺激试验表明，与传统的离子液体载体相比，新载体的毒性可以忽略不计。基于这些发现，我们认为基于SAIL[Cho][Ole]的MF具有作为生物相容性纳米载体的潜力，用于有效透皮递送难溶性化疗药物如PTX。
Chemotherapeutic cytotoxic agents such as paclitaxel (PTX) are considered essential for the treatment of various cancers. However, PTX injection is associated with severe systemic side effects and high rates of patient noncompliance. Micelle formulations (MFs) are nano-drug delivery systems that offer a solution to these problems. Herein, we report an advantageous carrier for the transdermal delivery of PTX comprising a new MF that consists of two biocompatible surfactants: cholinium oleate ([Cho][Ole]), which is a surface-active ionic liquid (SAIL), and sorbitan monolaurate (Span-20). A solubility assessment confirmed that PTX was readily solubilized in the SAIL-based micelles via multipoint hydrogen bonding and cation-p and p-p interactions between PTX and SAIL[Cho][Ole]. Dynamic light scattering (DLS) and transmission electron microscopy revealed that in the presence of PTX, the MF formed spherical PTX-loaded micelles that were well-distributed in the range 8.7-25.3 nm. According to DLS, the sizes and size distributions of the micelle droplets did not change significantly over the entire storage period, attesting to their physical stability. In vitro transdermal assessments using a Franz diffusion cell revealed that the MF absorbed PTX 4 times more effectively than a Tween 80-based formulation and 6 times more effectively than an ethanol-based formulation. In vitro and in vivo skin irritation tests revealed that the new carrier had a negligible toxicity profile compared with a conventional ionic liquid-based carrier. Based on these findings, we believe that the SAIL[Cho][Ole]-based MF has potential as a biocompatible nanocarrier for the effective transdermal delivery of poorly soluble chemotherapeutics such as PTX.