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用于劳拉西泮快速透皮递送的速溶微针的设计与配方

Design and formulation of fast-dissolving microneedles for the rapid transdermal delivery of lorazepam.

作者信息

M Punith, A J Rajamma, S B Sateesha, Diwakar Durgashree, E K Girija, K B Chethan Kumar, N A Ankith, Bhowmik Mousam, P M Manjunatha

机构信息

Department of Pharmaceutics, Acharya & BM Reddy College of Pharmacy, Bengaluru, India.

Department of Pharmacognosy, KLE College of Pharmacy, Bengaluru, India.

出版信息

J Drug Target. 2025 Sep;33(8):1399-1411. doi: 10.1080/1061186X.2025.2483720. Epub 2025 Apr 3.

Abstract

This study investigates lorazepam-loaded dissolving microneedles (LMNs) as a fast-acting and minimally invasive treatment for status epilepticus. The LMNs were developed using a micro-moulding technique with an optimised combination of PVP K30, Dextran 40 and Pullulan. Their stability was confirmed through Fourier transform infra-red (FTIR) spectroscopy and X-ray diffraction (XRD) analysis. The Parafilm membrane insertion test demonstrated 100% penetration efficiency, verifying their ability to effectively pierce the skin. Scanning electron microscopy (SEM) imaging revealed well-defined microneedles with precise dimensions (800 µm height, 200 µm base and 500 µm pitch). The LMNs rapidly dissolved in the subdermal layer of porcine skin. An drug diffusion study showed that 3-5% of the encapsulated lorazepam was released within 30 min, with a cumulative release of 79.3% over 24 h. An acute dermal irritation study confirmed the biocompatibility and skin tolerance of the LMNs. Additionally, an anti-convulsant efficacy study in Albino Wistar rats subjected to maximal electroshock seizures demonstrated significant anticonvulsant effects ( < .05), confirming efficient systemic delivery of lorazepam. These findings highlight LMNs as a rapid-acting, non-invasive transdermal drug delivery system for managing status epilepticus, particularly in ambulatory care settings.

摘要

本研究调查了载有劳拉西泮的溶蚀性微针(LMNs)作为癫痫持续状态的快速起效和微创治疗方法。LMNs采用微成型技术,使用聚乙烯吡咯烷酮K30、右旋糖酐40和支链淀粉的优化组合制成。通过傅里叶变换红外(FTIR)光谱和X射线衍射(XRD)分析证实了它们的稳定性。Parafilm膜插入试验显示穿透效率为100%,验证了其有效刺穿皮肤的能力。扫描电子显微镜(SEM)成像显示微针轮廓清晰,尺寸精确(高度800 µm,基部200 µm,间距500 µm)。LMNs在猪皮肤的皮下层迅速溶解。药物扩散研究表明,30分钟内释放了3-5%的封装劳拉西泮,24小时内累积释放率为79.3%。急性皮肤刺激性研究证实了LMNs的生物相容性和皮肤耐受性。此外,在接受最大电休克惊厥的白化Wistar大鼠中进行的抗惊厥疗效研究显示出显著的抗惊厥作用(P<0.05),证实了劳拉西泮的有效全身递送。这些发现突出了LMNs作为一种快速起效、非侵入性的透皮给药系统,用于治疗癫痫持续状态,特别是在门诊护理环境中。

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