Vacuum compression-molded polyvinyl alcohol microneedles for sustained three-day transdermal delivery of palonosetron hydrochloride.

IF 5.5 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Drug Delivery and Translational Research Pub Date : 2025-09-23 DOI:10.1007/s13346-025-01980-z

Meheli Ghosh, Sharvari M Kshirsagar, Thomas Kipping, Ajay K Banga

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引用次数: 0

Abstract

This study introduces vacuum compression molding (VCM) as a novel, solvent-free method for fabricating palonosetron hydrochloride (PAL HCl)-loaded polyvinyl alcohol (PVA) microneedles (MNs), addressing limitations of conventional micromolding such as extended drying times, batch variability, and solvent residues. PAL HCl-a hydrophilic 5-HT3 receptor antagonist (MW: 332.85 g/mol) with a low therapeutic dose-was selected for its clinical relevance in managing chemotherapy-induced nausea and vomiting (CINV). The microneedle platform offers advantages over PAL HCl's existing oral and injectable dosage forms, including pain-free application and improved patient compliance. The aim of this research is to develop and evaluate a scalable VCM-based fabrication approach for PAL HCl-loaded PVA microneedles, with the goal of achieving sustained, three-day in vitro transdermal drug delivery for improved CINV management. Ten PVA grades (varying in molecular weight and viscosity) were screened to optimize microneedle fabrication. Three formulations-M1 (particle-engineered PVA 4-88), M4 (PVA 5-88), and M5 (PVA 8-88)-demonstrated optimal mechanical strength, uniform geometry (SEM imaging), and reliable skin penetration (~ 200 μm depth in dermatomed human skin). Physicochemical characterization (FTIR, DSC) confirmed the amorphous state of PAL HCl within the PVA matrix and the absence of chemical interactions. In vitro release testing revealed biphasic profiles: an initial burst release for 8 h followed by sustained release over 72 h. Cumulative release inversely correlated with PVA molecular weight and viscosity, with M1 achieving 100% release, compared to M4 (74%) and M5 (67%). Permeation studies demonstrated M1's superior performance (257.56 ± 29.73 µg/sq cm), exceeding passive diffusion by 8.8-fold and significantly outperforming M4 (64.99 ± 30.23 µg/ sq cm) and M5 (39.03 ± 20.20 µg/sq cm). These results validate VCM as a scalable, tunable platform for fabricating PAL HCl-drug-loaded microneedles, offering sustained transdermal delivery with clinical potential for CINV management.

查看原文本刊更多论文

真空压缩成型聚乙烯醇微针持续三天的透皮给药盐酸帕洛诺司琼。

本研究介绍了真空压缩成型（VCM）作为一种新的、无溶剂的方法来制造盐酸帕洛诺西酮（PAL HCl）负载聚乙烯醇（PVA）微针（MNs），解决了传统微成型的局限性，如干燥时间延长、批次变化和溶剂残留。PAL hcl是一种低治疗剂量的亲水性5-HT3受体拮抗剂（分子量：332.85 g/mol），因其与化疗引起的恶心和呕吐（CINV）的临床相关性而被选中。与PAL HCl现有的口服和注射剂型相比，微针平台具有优势，包括无痛应用和提高患者依从性。本研究的目的是开发和评估一种可扩展的基于vcm的PVA微针制造方法，用于PAL hcl负载的PVA微针，目标是实现持续三天的体外透皮给药，以改善CINV的管理。筛选了十种不同分子量和粘度的PVA等级，以优化微针的制造。三种配方- m1（颗粒工程PVA 4-88）， M4 （PVA 5-88）和M5 (PVA 8-88)-表现出最佳的机械强度，均匀的几何形状（SEM成像）和可靠的皮肤穿透性（约200 μm深度的皮肤）。理化表征（FTIR， DSC）证实了PAL HCl在PVA基体中的无定形状态和不存在化学相互作用。体外释放测试显示出双相分布：初始爆发释放8小时，随后持续释放72小时。累积释放与PVA分子量和粘度呈负相关，M1达到100%释放，而M4（74%）和M5（67%）。渗透研究表明，M1的性能优于M4（64.99±30.23µg/sq cm）和M5(39.03±20.20µg/sq cm)(257.56±29.73µg/sq cm)，是被动扩散的8.8倍。这些结果验证了VCM是一种可扩展的、可调整的平台，用于制造PAL盐酸载药微针，提供持续的经皮给药，具有CINV治疗的临床潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY

CiteScore

11.70

自引率

1.90%

发文量

160

期刊介绍： The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.