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用于两性霉素B皮肤靶向的纳米脂质体制剂:体外和体内评估

Nanoethosomal formulation for skin targeting of amphotericin B: an in vitro and in vivo assessment.

作者信息

Kaur Lakhvir, Jain Subheet Kumar, Manhas Rajesh Kumari, Sharma Deepika

机构信息

a Department of Pharmaceutical Sciences , Guru Nanak Dev University , Amritsar , Punjab , India and.

b Department of Microbiology , Guru Nanak Dev University , Amritsar , Punjab , India.

出版信息

J Liposome Res. 2015;25(4):294-307. doi: 10.3109/08982104.2014.995670. Epub 2014 Dec 30.

DOI:10.3109/08982104.2014.995670
PMID:25547800
Abstract

The present study is envisaged to develop nanoethosomal formulation for enhanced topical delivery of amphotericin B (AmB) for the treatment of cutaneous fungal infections. AmB encapsulated nanoethosomes were prepared using mechanical dispersion method in a strength of 0.1% w/w similar to the strength of marketed topical formulation. Vesicle size of nanoethosomal formulations was found to be in the range of 186 ± 2 to 298 ± 4 nm. The optimized nanoethosomal formulation was further incorporated in gel base to form AmB nanoethogel formulation. Rheological characterization study of nanoethogel demonstrated its viscoelastic nature with high elasticity and resistance to deformation at 37 °C. The yield stress value was found to be 108.05 ± 2.4 and 52.15 ± 0.9 Pa for nanoethogel and marketed gel formulation, respectively. The nanoethogel formulation exhibited 2.7- and 3.5-fold higher steady state transdermal flux and skin deposition of AmB, respectively, in comparison to marketed formulation. Confocal laser scanning microscopy (CLSM) study also revealed enhanced skin permeation and deposition with nanoethogel formulation. In vivo study showed that topical application of nanoethogel does not exhibit any skin irritation as tested by Draize test. The developed formulation, in comparison to the marketed gel, demonstrated a remarkable increase in the antifungal activity against Candida albicans. It is thus corroborated from the above results that nanoethosomal formulation represents an efficacious carrier for effective topical delivery of AmB.

摘要

本研究旨在开发纳米脂质体剂型,以增强两性霉素B(AmB)的局部给药效果,用于治疗皮肤真菌感染。采用机械分散法制备了包封AmB的纳米脂质体,其浓度为0.1% w/w,与市售局部制剂的浓度相似。纳米脂质体制剂的囊泡大小在186±2至298±4nm范围内。将优化后的纳米脂质体制剂进一步加入凝胶基质中,制成AmB纳米脂质凝胶制剂。纳米脂质凝胶的流变学特性研究表明,其在37℃下具有高弹性和抗变形能力的粘弹性性质。纳米脂质凝胶和市售凝胶制剂的屈服应力值分别为108.05±2.4和52.15±0.9Pa。与市售制剂相比,纳米脂质凝胶制剂的AmB稳态透皮通量和皮肤沉积量分别高出2.7倍和3.5倍。共聚焦激光扫描显微镜(CLSM)研究还显示,纳米脂质凝胶制剂的皮肤渗透和沉积增强。体内研究表明,通过Draize试验测试,纳米脂质凝胶的局部应用未表现出任何皮肤刺激性。与市售凝胶相比,所开发的制剂对白色念珠菌显示出显著增强的抗真菌活性。因此,从上述结果可以证实,纳米脂质体制剂是AmB有效局部给药的有效载体。

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