University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Int J Pharm. 2012 Nov 1;437(1-2):277-87. doi: 10.1016/j.ijpharm.2012.08.015. Epub 2012 Aug 19.
The present study is aimed at the encapsulation of griseofulvin in the deformable membrane vesicles (DMVs) for dermal delivery. Presently, griseofulvin is available only in conventional oral dosage forms that suffer from the issues of poor and highly variable bioavailability, numerous systemic side effects and long duration of treatment. Multi-lamellar drug-loaded DMVs of griseofulvin (Indian Patent Application 208/DEL/2009) were prepared by thin-film hydration method and were optimized for type and concentration of edge activator (EA). The optimized formulation was evaluated for vesicular shape, size, drug entrapment efficiency, drug content, pH, stability, spreadability, ex vivo skin permeation, dermatokinetics, skin sensitivity, in vitro antifungal assay and in vivo antifungal activity against Microsporum canis using guinea pig model for dermatophytosis. The optimized DMVs illustrated remarkably higher drug permeation and skin retention when compared with liposomes. A complete clinical and mycological cure was observed in animals treated with topical griseofulvin formulation in 10 days. The formulation was observed to be non-sensitizing, histopathologically safe, and stable at 5±3 °C, 25±2 °C and 40±2 °C for a period of six months. The results indicated that the topical formulation of DMVs of griseofulvin could be utilized as an alternative to reduce the encumbrance of conventional oral formulations.
本研究旨在将灰黄霉素封装在变形膜囊泡(DMVs)中用于皮肤递药。目前,灰黄霉素仅可通过常规口服剂型获得,但存在生物利用度差且变异性大、多种全身副作用和治疗时间长等问题。灰黄霉素多层层载药 DMVs(印度专利申请 208/DEL/2009)通过薄膜水化法制备,并对边缘活性剂(EA)的类型和浓度进行了优化。对优化后的配方进行了囊泡形态、粒径、药物包封效率、药物含量、pH 值、稳定性、铺展性、体外皮肤渗透、皮肤药代动力学、皮肤敏感性、体外抗真菌活性和体内抗真菌活性(针对小孢子菌感染豚鼠模型)评估。与脂质体相比,优化后的 DMVs 显示出显著更高的药物渗透和皮肤滞留。经皮给予灰黄霉素制剂的动物在 10 天内完全临床和真菌学治愈。该制剂在 5±3°C、25±2°C 和 40±2°C 下 6 个月内稳定,无致敏性,组织病理学安全。结果表明,灰黄霉素 DMVs 的局部制剂可替代常规口服制剂,以减轻其负担。