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Abstract：
Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate (ODHP) was extracted in a previous study from the culture broth of soil isolate Alcaligenes faecalis MT332429 and showed a promising antimycotic activity. This study was aimed to formulate ODHP loaded β-cyclodextrins (CD) nanosponge (NS) hydrogel (HG) to control skin fungal ailments since nanosponges augment the retention of tested agents in the skin. Box-Behnken design was used to produce the optimized NS formulation, where entrapment efficiency percent (EE%), polydispersity index (PDI), and particle size (PS) were assigned as dependent parameters, while the independent process parameters were polyvinyl alcohol % (w/v %), polymer-linker ratio, homogenization time, and speed. The carbopol 940 hydrogel was then created by incorporating the nanosponges. The hydrogel fit Higuchi\'s kinetic release model the best, according to in vitro drug release. Stability and photodegradation studies revealed that the NS-HG remained stable under tested conditions. The formulation also showed higher in vitro antifungal activity against Candida albicans compared to the control fluconazole. In vivo study showed that ODHP-NS-HG increased survival rates, wound contraction, and healing of wound gap and inhibited the inflammation process compared to the other control groups. The histopathological examinations and Masson\'s trichrome staining showed improved healing and higher records of collagen deposition. Moreover, the permeability of ODHP-NS-HG was higher through rats\' skin by 1.5-folds compared to the control isoconazole 1%. Therefore, based on these results, NS-HG formulation is a potential carrier for enhanced and improved topical delivery of ODHP. Our study is a pioneering research on the development of a formulation for ODHP produced naturally from soil bacteria. KEY POINTS: • Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate was successfully formulated as a nanosponge hydrogel and statistically optimized. • The new formula exhibited in vitro good stability, drug release, and higher antifungal activity against C. albicans as compared to the fluconazole. • Ex vivo showed enhanced skin permeability, and in vivo analysis showed high antifungal activity as evidenced by measurement of various biochemical parameters and histopathological examination.
摘要：
在先前的研究中，从土壤分离粪产碱杆菌MT332429的培养液中提取了3-（3,5-二叔丁基-4-羟基苯基）丙酸十八烷基酯（ODHP），并显示出有希望的抗真菌活性。这项研究旨在配制ODHP负载的β-环糊精（CD）纳米海绵（NS）水凝胶（HG）以控制皮肤真菌疾病，因为纳米海绵可增强测试剂在皮肤中的保留。Box-Behnken设计用于生产优化的NS配方，其中截留效率百分比(EE%)，多分散指数(PDI)，和粒度(PS)被指定为相关参数，而独立的工艺参数为聚乙烯醇%(w/v%)，聚合物-接头比，均质化时间，和速度。然后通过掺入纳米海绵来产生卡波姆940水凝胶。水凝胶拟合Higuchi的动力学释放模型最好，根据体外药物释放。稳定性和光降解研究表明，NS-HG在测试条件下保持稳定。与对照氟康唑相比,该制剂还对白色念珠菌显示出更高的体外抗真菌活性。体内研究表明，ODHP-NS-HG可提高生存率，伤口收缩,与其他对照组相比，伤口间隙愈合并抑制炎症过程。组织病理学检查和Masson三色染色显示愈合改善，胶原蛋白沉积记录较高。此外，ODHP-NS-HG通过大鼠皮肤的通透性比对照异康唑1%高1.5倍。因此,基于这些结果，NS-HG制剂是用于增强和改善ODHP的局部递送的潜在载体。我们的研究是关于开发由土壤细菌自然产生的ODHP配方的开创性研究。关键点:•3-(3,5-二叔丁基-4-羟基苯基)丙酸十八烷基酯被成功地配制成纳米海绵水凝胶并进行统计学优化。•新配方表现出良好的体外稳定性，药物释放，和对白色念珠菌的抗真菌活性高于氟康唑。•离体显示皮肤渗透性增强,和体内分析显示出高抗真菌活性，如各种生化参数的测量和组织病理学检查所证明。
