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载阿昔洛韦的柔性膜囊泡(FMVs)的制备:在 HSV-1 感染皮肤的鼠模型中抗病毒活性的临床前疗效的证据。

Fabrication of acyclovir-loaded flexible membrane vesicles (FMVs): evidence of preclinical efficacy of antiviral activity in murine model of cutaneous HSV-1 infection.

机构信息

University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160014, India.

Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

出版信息

Drug Deliv Transl Res. 2017 Oct;7(5):683-694. doi: 10.1007/s13346-017-0417-0.

Abstract

The present investigation focuses on the development and evaluation of acyclovir-loaded flexible membrane vesicles (ACY-FMVs) and evaluates their targeting potential to localize the drug into skin layers. The drug-loaded FMVs were prepared by thin-film hydration method and characterized for various attributes including micromeritics, entrapment efficiency, vesicle shape, size, and degree of deformability. The values of particle size and zeta potential of the developed carrier system were found to be 453.7 nm and - 11.62 mV, respectively. The system was further incorporated into a hydrogel and evaluated for skin permeability and retention characteristics in comparison to marketed formulation. The developed formulation demonstrated enhanced retention of drug deep inside the skin layers which can probably decrease the frequency of application of the drug, thereby reducing its adverse effects. Skin irritancy studies performed on Laca mice skin proved the safety and non-irritant nature of ACY-FMVs. The pharmacodynamic studies on murine model for HSV-1 infection demonstrated immense potential and safety of topically applied ACY-FMVs. However, more intensive studies need to be pursued to explore and exploit the potential of lipid-based systems in anti-viral therapeutics. These preclinical findings provide a hope for corroborating the efficacy in clinical situations.

摘要

本研究关注的是负载阿昔洛韦的柔性膜囊泡(ACY-FMVs)的开发和评估,并评估其将药物靶向定位到皮肤层的潜力。载药 FMVs 通过薄膜水化法制备,并对各种特性进行了表征,包括微尺度、包封效率、囊泡形状、大小和变形程度。所开发的载体系统的粒径和 Zeta 电位值分别为 453.7nm 和-11.62mV。该系统进一步被整合到水凝胶中,并与市售制剂进行了皮肤渗透性和保留特性的评估。与市售制剂相比,开发的制剂表现出药物在皮肤深层的滞留能力增强,这可能会降低药物的应用频率,从而减少其不良反应。在 Laca 小鼠皮肤上进行的皮肤刺激性研究证明了 ACY-FMVs 的安全性和非刺激性。针对 HSV-1 感染的小鼠模型进行的药效学研究表明,局部应用 ACY-FMVs 具有巨大的潜力和安全性。然而,需要进行更多的深入研究,以探索和利用基于脂质的系统在抗病毒治疗中的潜力。这些临床前研究结果为在临床情况下证实疗效提供了希望。

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