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

Abstract

Muhammad Khalid Khan,1 Barkat Ali Khan,1 Bushra Uzair,2 Shah Iram Niaz,3 Haroon Khan,4 Khaled Mohamed Hosny,5 Farid Menaa6 1Drug Delivery and Cosmetics Laboratory (DDCL), Faculty of Pharmacy, Gomal University, Dera Ismail Khan, 29050, Pakistan; 2Department of Biotechnology and Bioinformatics, International Islamic University, Islamabad, 40000, Pakistan; 3Department of Chemistry, Institute of Chemical Sciences, Gomal University, Dera Ismail Khan, 29050, Pakistan; 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gomal University, Dera Ismail Khan, 29050, Pakistan; 5Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 6Department of Nanomedicine, California Innovations Corporation, San Diego, CA, 92037, USACorrespondence: Muhammad Khalid Khan Email [email protected]: 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) 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.Keywords: fungal resistance, red soil, Pseudomonas fluorescens, microbial secondary metabolites, phthalic acid ester derivative, nanoemulsion gel

Keywords

• fungal resistance
• red soil
• pseudomonas fluorescens
• microbial secondary metabolites
• phthalic acid ester derivative
• nanoemulsion gel.