Optimized albendazole-loaded nanostructured lipid carrier gel: a redefined approach for localized skin cancer treatment†

Chinmayee Khot, Kaustubh Kolekar, Swati Dabhole, Akshay Mohite, Sameer Nadaf, Popat S. Kumbhar and John Disouza
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Abstract

The chief purpose of the current study is to fabricate nanostructured lipid carrier (NLC)-based gel for localized delivery of repurposed albendazole (ABZ) against skin cancer to reduce systemic and other organ-related side effects and enhance patient compliance. ABZ NLCs were constructed by the melt-emulsification ultrasonication method and optimized using Box-Behnken Design (BBD). The ABZ NLCs were analyzed for mean particle size, % entrapment efficiency (%EE), and zeta potential. Furthermore, an NLC-based gel was developed using optimized ABZ NLCs and the Carbopol-934 gelling agent and characterized for physical properties, viscosity, texture, ex vivo skin permeation, in vitro cytotoxicity, stability, etc. The optimized ABZ NLCs displayed a %EE of 89.85 ± 5.6% and a particle size of 176.5 ± 7.3 nm. The pH of the ABZ NLC-based gel developed using 1.0% w/v of Carbopol-934 was between 5.1 and 6.0. The viscosity of the optimized ABZ NLC-based gel was 6.64 ± 0.67 Pa s. Besides, the NLC-based gel exhibited better and controlled ABZ release at pH 5.5 and 6.8 than the conventional ABZ gel. The ex vivo permeation of ABZ from NLCs and the NLC-based gel was 5.1 and 4.5-fold higher, respectively, than from the conventional gel. Notably, the in vitro cytotoxicity against B16F10 cells of ABZ NLCs was 1.7-fold and 2.2-fold higher than those of pure ABZ and the ABZ NLC-based gel. A negligible cytotoxicity of the developed formulations was seen in normal HaCaT cells (human epidermal cells), signifying the compatibility of these formulations with healthy cells. Moreover, the ABZ-incorporated NLCs and NLC gel remained stable for twelve weeks at 4 ± 2 °C. Thus, the given research concludes that the NLC-loaded gel could be a harmless, efficient, and novel choice to treat skin cancer using repurposed ABZ.

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优化阿苯达唑负载纳米结构脂质载体凝胶:一种重新定义的局部皮肤癌治疗方法
本研究的主要目的是制造基于纳米结构脂质载体(NLC)的凝胶,用于局部递送靶向治疗皮肤癌的阿苯达唑(ABZ),以减少全身和其他器官相关的副作用,并提高患者的依从性。采用熔融乳化超声法制备ABZ型NLCs,并采用Box-Behnken设计(BBD)进行优化。分析了ABZ NLCs的平均粒径、%捕获效率(%EE)和zeta电位。利用优化后的ABZ nlc和carbpol -934凝胶剂制备了一种基于nlc的凝胶,并对其物理性能、粘度、质地、体外皮肤渗透、体外细胞毒性、稳定性等进行了表征。优化后的ABZ NLCs的EE为89.85±5.6%,粒径为176.5±7.3 nm。用1.0% w/v的carbpol -934制备的ABZ nlc基凝胶的pH值在5.1 ~ 6.0之间。优化后的ABZ nlc凝胶黏度为6.64±0.67 Pa s,且在pH为5.5和6.8时ABZ的释放优于常规ABZ凝胶。NLCs和基于NLCs的凝胶对ABZ的体外渗透分别比传统凝胶高5.1倍和4.5倍。值得注意的是,ABZ nlc对B16F10细胞的体外细胞毒性分别比纯ABZ和ABZ nlc凝胶高1.7倍和2.2倍。在正常HaCaT细胞(人表皮细胞)中发现了可忽略不计的细胞毒性,这表明这些配方与健康细胞的相容性。此外,abz结合的NLC和NLC凝胶在4±2°C下保持稳定12周。因此,本研究得出结论,负载nlc的凝胶可能是一种无害、有效和新颖的选择,可以使用重新利用的ABZ治疗皮肤癌。
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