Ultrasmall Polymeric Micelles Enable Noninvasive Transdermal Rosiglitazone Delivery via Lipid Fluidization and Transcytosis

IF 5.9 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2026-09-14 Epub Date: 2026-08-28 DOI:10.1021/acs.biomac.6c00656

Yuan Wang, Songmei Luo, Lu Wang, Yansong Zhang, Ruhui Yang, Yuhao Jiang, Jingjing Guo, Xingjie Zan, Sicheng Tang, Kejun Cheng

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Abstract

Noninvasive transdermal drug delivery (TDD) offers sustained therapeutic release but is hindered by the stratum corneum (SC) barrier. Herein, we report ultrasmall polymeric micelles (PMs) embedded in poly(vinyl alcohol) hydrogels for the passive TDD of rosiglitazone (RGT) to treat Type 2 diabetes mellitus (T2DM). We synthesized amphiphilic brush copolymers with varied hydrophobic cores (linear alkanes, benzene, borneol) to tune SC interactions and ensure colloidal stability. Ex vivo murine skin studies demonstrated that PM variants with C10 alkane and benzene cores achieved 10.56% and 19.84% cumulative permeation at 24 h, respectively, via dual paracellular/intracellular routes. In vivo, PM hydrogels delivered steady plasma accumulation. In a T2DM model, transdermal RGT reduced blood glucose by 30% over 12 days without observable skin or organ toxicity. This nanoplatform enables noninvasive systemic delivery, offering a robust alternative to oral administration for sustained glycemic control.

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查看原文本刊更多论文

超小聚合物胶束通过脂质流化和胞吞作用实现罗格列酮的无创透皮递送

无创经皮给药（TDD）提供持续的药物释放，但受到角质层（SC）屏障的阻碍。在此，我们报道了嵌入聚乙烯醇水凝胶中的超小聚合物胶束（pm）用于罗格列酮（RGT）治疗2型糖尿病（T2DM）的被动TDD。我们合成了具有不同疏水核心（线性烷烃、苯、冰片）的两亲性电刷共聚物，以调节SC相互作用并确保胶体稳定性。体外小鼠皮肤研究表明，具有C10烷烃和苯核的PM变体通过细胞外/细胞内双重途径，24小时的累积渗透率分别达到10.56%和19.84%。在体内，PM水凝胶提供稳定的血浆积累。在t2dm模型中，经皮RGT在12天内降低了30%的血糖，没有观察到皮肤或器官毒性。该纳米平台可实现无创全身给药，为持续血糖控制提供了口服给药的强大替代方案。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.