Innovative transdermal delivery of microneedle patch for dual drugs febuxostat and lornoxicam: In vitro and in vivo efficacy for treating gouty arthritis

IF 4.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology Pub Date : 2025-05-19 DOI:10.1016/j.jddst.2025.107053

Sammar Fathy Elhabal , Hossam Abdo Ashour , Mohamed Fathi Mohamed Elrefai , Mahmoud H. Teaima , Nahla A. Elzohairy , Nada ahmed kholeif , Mohamed El-Nabarawi

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引用次数: 0

Abstract

Gouty arthritis (GA) is a kind of joint disease caused by the deposition of monosodium urate (MSU) crystals. Anti-inflammatory and uric acid-lowering treatments are necessary for GA patients on a long-term basis. Febuxostat (Feb), a selective xanthine oxidase inhibitor, with a moderate F value (<49 %). Lornoxicam (Lor) is a potent nonsteroidal anti-inflammatory drug (NSAID) that is widely used to treat pain and inflammation. However, both drugs belong to BCS class II, showing low solubility and high permeability. This study presents a microneedle (MN) patch for the co-delivery of Febuxostat and Lornoxicam to tackle the challenges associated with gouty arthritis treatment. The optimized microneedle patch with a biodegradable polyvinyl alcohol (PVA)/polyvinylpyrrolidone (PVP), polyethene glycol (PEG 400) matrix and chitosan backing worked well both in vitro and in vivo study. Lornoxicam and Febuxostat were released at 99 % and 100 %, respectively, in vitro, within 48 h. The microneedles were strong enough to withstand 1000 g but disintegrated within minutes of skin contact. In vivo studies utilizing a hyperuricemia rat model demonstrated that the microneedle patch decreased serum uric acid levels by 85.4 % and inhibited xanthine oxidase activity in the serum and liver by 72.4 % and 68.3 %, respectively. The patch significantly reduced inflammatory markers like MMP-3, CRP, TNF-α, and IL-1β, demonstrating its anti-inflammatory properties. Histopathological analysis showed greater joint and hepatic architecture restoration and inflammation reduction than conventional formulations. This novel microneedle patch delivery method outperformed oral and gel-based drug delivery methods in bioavailability, therapeutic effects, and systemic side effects. These results demonstrate the microneedle-based system's potential as an innovative and patient-friendly, gouty arthritis treatment.

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非布司他和氯诺昔康双药微针贴片经皮给药：治疗痛风性关节炎的体内外疗效

痛风性关节炎（GA）是一种由尿酸钠（MSU）晶体沉积引起的关节疾病。抗炎和降尿酸治疗是GA患者长期治疗的必要条件。非布司他（Feb），选择性黄嘌呤氧化酶抑制剂，F值适中（49%）。氯诺昔康（Lor）是一种有效的非甾体抗炎药（NSAID），广泛用于治疗疼痛和炎症。然而，这两种药物都属于BCS II类，具有低溶解度和高通透性。本研究提出了一种微针（MN）贴片，用于联合递送非布司他和氯诺昔康，以解决痛风性关节炎治疗相关的挑战。以可生物降解聚乙烯醇(PVA)/聚乙烯吡罗烷酮（PVP）、聚乙二醇（peg400）为基质，壳聚糖为衬底的微针贴片体外和体内实验均取得了良好的效果。氯诺昔康和非布司他在体外48小时内分别以99%和100%的速度释放。微针的强度足以承受1000 g，但在皮肤接触几分钟内就会分解。利用高尿酸血症大鼠模型进行的体内研究表明，微针贴片可使血清尿酸水平降低85.4%，并使血清和肝脏中的黄嘌呤氧化酶活性分别降低72.4%和68.3%。该贴片可显著降低炎症标志物，如MMP-3、CRP、TNF-α和IL-1β，显示其抗炎特性。组织病理学分析显示，与传统配方相比，该配方更能恢复关节和肝脏的结构，减少炎症。这种新型的微针贴片给药方法在生物利用度、治疗效果和全身副作用方面优于口服和凝胶给药方法。这些结果证明了微针系统作为一种创新的、对患者友好的痛风性关节炎治疗方法的潜力。

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

Journal of Drug Delivery Science and Technology 医学-药学

CiteScore

8.00

自引率

8.00%

发文量

879

审稿时长

94 days

期刊介绍： The Journal of Drug Delivery Science and Technology is an international journal devoted to drug delivery and pharmaceutical technology. The journal covers all innovative aspects of all pharmaceutical dosage forms and the most advanced research on controlled release, bioavailability and drug absorption, nanomedicines, gene delivery, tissue engineering, etc. Hot topics, related to manufacturing processes and quality control, are also welcomed.