El-Sayed Sayed E, Abdelaziz Neveen A, El-Housseiny Ghadir S, Aboshanab Khaled M
Department of Microbiology and Immunology, Faculty of Pharmacy, Sixth of October City, Ahram Canadian University, 6 October city, Giza, 12451, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.
Microb Cell Fact. 2025 Apr 1;24(1):77. doi: 10.1186/s12934-025-02688-y.
In a previous study, 6-methoxy-1 H-indole-2-carboxylic acid (MICA) was isolated from the culture broth of Bacillus toyonensis strain OQ071612 soil isolate in our laboratory, and it demonstrated promising antifungal activities. The current study was designed to create a nanosponge (NS)-hydrogel (HG)-containing MICA followed by in vitro and preclinical evaluation for potential clinical use in the topical treatment of mycotic infections.
The enhanced NS formula was created using the Box Behnken Design (BBD), with independent process parameters including polyvinyl alcohol percentage (w/v%), homogenization time, speed and polymer: linker ratio. Dependent parameters were particle size (PS), polydispersity index (PDI), and entrapment efficiency percent (EE%). A hydrogel was formulated from the NS. In vitro drug release data indicated that the hydrogel best matched Higuchi's kinetic release model. The formulated NS-HG was stable and when compared to fluconazole, it exhibited increased antimycotic activity against C. albicans. An in vivo investigation revealed that MICA-NS-HG enhanced survival rates, wound gap repair, wound reduction, and inflammation inhibition. Masson's trichrome staining and histological analyses revealed increased collagen deposition and improved healing. Moreover, MICA hydrogel exhibited 1.5-fold greater permeability through rat skin compared to the control, 1% isoconazole.
The NS-HG formulation is a viable vehicle for better and more effective topical release of MICA. These findings represent a significant advancement in the formulation of MICA derived from naturally occurring soil bacteria.
在之前的一项研究中，我们实验室从土壤分离的东洋芽孢杆菌菌株OQ071612的培养液中分离出了6-甲氧基-1H-吲哚-2-羧酸（MICA），它显示出有前景的抗真菌活性。本研究旨在制备含MICA的纳米海绵（NS）-水凝胶（HG），然后进行体外和临床前评估，以确定其在局部治疗真菌感染方面的潜在临床应用价值。
采用Box Behnken设计（BBD）创建了增强型NS配方，独立的工艺参数包括聚乙烯醇百分比（w/v%）、均质化时间、速度以及聚合物与连接剂的比例。相关参数为粒径（PS）、多分散指数（PDI）和包封率百分比（EE%）。由NS制备了一种水凝胶。体外药物释放数据表明，该水凝胶最符合Higuchi动力学释放模型。所制备的NS-HG稳定，与氟康唑相比，它对白色念珠菌表现出增强的抗真菌活性。体内研究表明，MICA-NS-HG提高了存活率、促进了伤口间隙修复、减小了伤口面积并抑制了炎症。Masson三色染色和组织学分析显示胶原沉积增加且愈合得到改善。此外，与对照1%异康唑相比，MICA水凝胶透过大鼠皮肤的渗透率高1.5倍。
NS-HG配方是一种可行的载体，可实现MICA更好、更有效的局部释放。这些发现代表了源自天然土壤细菌的MICA制剂的重大进展。
