State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, China.
Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
ACS Appl Bio Mater. 2024 Jun 17;7(6):4051-4061. doi: 10.1021/acsabm.4c00399. Epub 2024 May 24.
Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.
高脂血症一直是全球健康的巨大挑战,导致心血管疾病、高血压和糖尿病。阿托伐他汀钙(AC)是一种广泛用于治疗高脂血症的药物,但由于其水溶性差和肝脏首过效应,口服给药面临巨大挑战,导致治疗效果不佳。在这项工作中,我们设计并开发了一种混合微针(MN)贴片系统,该系统由可溶的聚乙烯醇(PVA)和载有 AC 的聚合物胶束(AC@PMs)构建,用于经皮递送 AC,以增强高脂血症的治疗效果。我们首先使用透析法从 mPEG-PLA 和 mPEG-PLA-PEG 嵌段共聚物制备了各种 AC@PM 制剂,并结合实验技能和耗散粒子动力学(DPD)模拟评估了它们的物理化学性质。然后,我们使用微模填充法将 AC@PMs 封装到 PVA MN 贴片,随后对其性能,特别是结构稳定性、机械性能和生物安全性进行了表征。在使用高脂血症大鼠模型进行体内实验后,我们的研究结果表明,与口服给药方法相比,混合微针介导的给药具有更好的治疗效果。总之,我们成功开发了一种混合微针(MN)贴片系统,为疏水性药物的高效经皮递送提供了有前景的潜力。
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