同轴纳米纤维中的纳米胶束作为戒烟的透皮给药平台：带有出口通道的同轴纳米纤维中的纳米胶束作为戒烟的透皮给药平台。

Nanomicelles-in-coaxial nanofibers with exit channels as a transdermal delivery platform for smoking cessation.

机构信息

Nanomedicine Lab, Center for Materials Science (CMS), Zewail City of Science and Technology, 6th of October, Giza 12578, Egypt.

Pharmaceutical Chemistry Department, National Organization for Drug Control and Research (NODCAR), Giza, Egypt.

出版信息

J Mater Chem B. 2022 Jul 6;10(26):4984-4998. doi: 10.1039/d2tb00818a.

DOI:10.1039/d2tb00818a

PMID:35708499

Abstract

Smoking is a life-threatening habit; that is why many nicotine-replacement therapies (NRTs), which include chewing gums, nicotine patches, lozenges, mouth sprays, inhalers and nasal sprays that are usually administered for 8-12 weeks, have been reported for smoking cessation. We report the fabrication of patches comprising nanomicelles-in-coaxial nanofibers (NFs) for the transdermal delivery of varenicline (VAR) tartrate, a partial agonist of the α4β2 receptor subtype, for smoking cessation. The cores of the fabricated coaxial NF structures are composed of polyethylene oxide, VAR-loaded Pluronic F127 nanomicelles (NPs) and free VAR, while the shell consists of a blend of cellulose acetate (CA) and polycaprolactone (PCL) in a ratio of 1 : 9 (w/w) that incorporates 50% (wt%) free VAR. The morphology and the coaxial structure of the NFs were investigated using TEM, SEM and fluorescent microscopy. The physicochemical and mechanical properties of the scaffolds were analyzed using FTIR, DSC, DLS, TGA and a universal testing machine. SEM micrographs depict NFs with a size ranging from 793.7 ± 518.9 to 324.5 ± 144.1 nm. release of VAR reaches almost 100% after 3, 9 and 28 days for free VAR, VAR-loaded NPs and the NPs-in-NFs patches, respectively, while the release tested using albino rat skin, over a period of 60 days, showed up to 94% sustained release of VAR. Besides, skin permeation, release and plasma concentrations of VAR from the NF transdermal patches were monitored cyclic voltammetric measurements during the course of treatment. DFT calculations as well as mathematical release kinetic models were performed in order to study the release mechanism. The cell viability of human skin fibroblast (HSF) cells in the case of plain and VAR-loaded NFs was 75.09 and 32.11%, respectively. The results showed that VAR was being continuously released from the transdermal patch over a period of 14 days. Besides, the treatment with VAR-loaded patches did not cause any severe conditions in the studied animal model. The new fabricated NPs-in-NFs transdermal patch for VAR tartrate delivery is considered as an effective, economic, safe and long-acting NRT for smoking cessation.

摘要

吸烟是一种危及生命的习惯；这就是为什么许多尼古丁替代疗法（NRT），包括咀嚼胶、尼古丁贴片、含片、口腔喷雾、吸入器和鼻喷雾剂，通常使用 8-12 周，被报道用于戒烟。我们报告了一种贴片的制造，该贴片由纳米胶束同轴纳米纤维（NFs）组成，用于经皮递varenicline（VAR）酒石酸盐，一种α4β2 受体亚型的部分激动剂，用于戒烟。所制造的同轴 NF 结构的核心由聚氧化乙烯、载有 VAR 的 Pluronic F127 纳米胶束（NPs）和游离 VAR 组成，而外壳由醋酸纤维素（CA）和聚己内酯（PCL）的混合物组成，比例为 1：9（w/w），其中包含 50%（wt%）的游离 VAR。使用 TEM、SEM 和荧光显微镜研究了 NFs 的形态和同轴结构。使用 FTIR、DSC、DLS、TGA 和万能试验机分析了支架的物理化学和机械性能。SEM 显微照片描绘了 NF 的尺寸范围从 793.7±518.9 到 324.5±144.1nm。游离 VAR 的释放在 3、9 和 28 天后分别达到近 100%，而载有 NPs 和 NPs 在内的 NF 贴片的 VAR 释放分别达到近 100%，而用白化大鼠皮肤测试，在 60 天的时间内，VAR 的持续释放达到 94%。此外，在治疗过程中，通过循环伏安法测量监测了 NF 透皮贴片中 VAR 的皮肤渗透、释放和血浆浓度。为了研究释放机制，进行了密度泛函理论（DFT）计算和数学释放动力学模型。在载有 VAR 的 NF 的情况下，人皮肤成纤维细胞（HSF）细胞的细胞活力分别为 75.09%和 32.11%。结果表明，VAR 正在从透皮贴片中持续释放，持续 14 天。此外，用载有 VAR 的贴片治疗不会在研究的动物模型中引起任何严重的情况。新制造的用于 VAR 酒石酸盐递送的 NPs 同轴 NF 透皮贴剂被认为是一种有效的、经济的、安全的、长效的戒烟尼古丁替代疗法。