Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations

Int J Nanomedicine. 2021 Dec 16;16:8203-8219. doi: 10.2147/IJN.S338064. eCollection 2021.


PURPOSE: Microbial resistance to antibiotics is one of the most important public health concerns of the 21st century. We isolated, purified, and structurally elucidated antifungal secondary metabolites from red soil microbes and encapsulated them into chitosan (CS)-based nanoemulsion (NE) gel (NEG).

METHODS: Three compounds were isolated and purified of which only one compound (Pure 2) showed potent antifungal activity (MFC: 8-132 µg/mL), which was also significantly (P<0.05) more efficient than fluconazole (MFC: 32-132 µg/mL). Pure 2 was structurally elucidated using 1D- and 2D-NMR before its incorporation into NEG. The formulations were prepared by high-speed homogenization technique. Physicochemical and pharmacological characterizations of formulations (ie, droplet size, PDI, zeta potential, drug content, viscosity, SEM, FTIR, spreadability, in vitro drug release, ex vivo permeation, in vitro antifungal and in vivo antifungal activities) were assessed.

RESULTS: NMR analyses identified the compound as a derivative of phthalic acid ester (PAE). The optimized formulations displayed a droplet size <100 nm, -ve zeta potential, and PDI <0.45. The drug content was within the official limit of pharmacopeia (ie, 100±10%). Insignificant changes (P>0.05) in the viscosity of the formulations stored were observed. The morphology of the formulations indicated mesh-like structure. The FTIR study indicated that there were no interactions between the drug and other ingredients of the formulations. Optimum spreadability was observed in all formulations. NEG released 75.3±1.12% of Pure 2 after 12 hrs while NE released 85.33±1.88% of the compound. The skin permeation of F2 (71.15±1.28%) was significantly different (P<0.05) from F3 (81.80±1.91%) in rabbits. Complete and apparently safe recovery from the fungal infection was achieved in rabbits treated topically with Pure 2-loaded NEGs.

CONCLUSION: Hence, the NEG-loaded PAE isolated from Pseudomonas fluorescens represents a possible alternative for the treatment of fungal infections as compared to available therapies.

PMID:34949923 | PMC:PMC8689013 | DOI:10.2147/IJN.S338064


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