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用于皮肤癌局部给药的马钱子碱负载转脂质体纳米凝胶:统计优化、体外及皮肤动力学评价

Brucine-loaded transliposomes nanogel for topical delivery in skin cancer: statistical optimization, in vitro and dermatokinetic evaluation.

作者信息

Alhakamy Nabil A, Aldawsari Hibah M, Ali Javed, Gupta Dipak K, Warsi Musarrat H, Bilgrami Anwar L, Asfour Hani Z, Noor Ahmad O, Md Shadab

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589 Saudi Arabia.

Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, 21589 Saudi Arabia.

出版信息

3 Biotech. 2021 Jun;11(6):288. doi: 10.1007/s13205-021-02841-5. Epub 2021 May 22.

Abstract

The aim of the present study was to develop, optimize brucine-loaded transliposomes (BRC-TL) formulation for dermal delivery of brucine for skin cancer. The BRC-TL formulations were evaluated for vesicle size, entrapment efficiency, and in vitro drug release. The optimized formulation was further evaluated for skin penetration by confocal laser microscopy and dermatokinetic study. The optimized BRC-TL formulation presented sealed lamellar shaped vesicles, with vesicles size, polydispersity index, entrapment efficiency, and in vitro drug release of 136.20 ± 2.87 nm, 0.354 ± 0.02, 86.01 ± 1.27%, and 83.09 ± 2.07%, respectively. Ex vivo permeation study showed that, developed BRC-TL formulation had a 2.4-fold increment in permeation as compared to BRC suspension. Texture analysis showed that the BRC-TL gel presented firmness of 158.91 g, consistency of 615.03 g/s, cohesiveness of  - 115.26 g and a viscosity index of  - 472.05 g/s. The confocal images of rat skin clearly showed the deeper penetration of rhodamine B-loaded TL formulation as compared to the Rhodamine B-hydro alcoholic solution. The optimized BRC-TL formulation demonstrated significantly higher cytotoxicity than placebo liposome and BRC suspension ( < 0.05). Further, the BRC-TL nanogel treated rat skin showed a substantial increase in C and AUC in comparison to rat skin treated with BRC conventional gel ( < 0.05). The data revealed that the developed TLs formulation could be a promising drug nanocarrier for brucine dermal delivery in the treatment of skin cancer.

摘要

本研究的目的是开发并优化用于皮肤癌治疗的、负载马钱子碱的转脂质体(BRC-TL)制剂,以实现马钱子碱的皮肤给药。对BRC-TL制剂的囊泡大小、包封率和体外药物释放进行了评估。通过共聚焦激光显微镜和皮肤动力学研究对优化后的制剂进行了进一步的皮肤渗透评估。优化后的BRC-TL制剂呈现出密封的层状囊泡,其囊泡大小、多分散指数、包封率和体外药物释放分别为136.20±2.87 nm、0.354±0.02、86.01±1.27%和83.09±2.07%。体外渗透研究表明,与BRC悬浮液相比,所开发的BRC-TL制剂的渗透率提高了2.4倍。质地分析表明,BRC-TL凝胶的硬度为158.91 g,稠度为615.03 g/s,内聚性为 -115.26 g,粘度指数为 -472.05 g/s。大鼠皮肤的共聚焦图像清楚地显示,与罗丹明B氢醇溶液相比,负载罗丹明B的TL制剂的渗透更深。优化后的BRC-TL制剂表现出比安慰剂脂质体和BRC悬浮液更高的细胞毒性(P<0.05)。此外,与用BRC传统凝胶处理的大鼠皮肤相比,用BRC-TL纳米凝胶处理的大鼠皮肤的C和AUC显著增加(P<0.05)。数据表明所开发的TL制剂可能是一种有前景的药物纳米载体,用于马钱子碱的皮肤给药以治疗皮肤癌。

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