Halal Alternative Formulation to Enhance Sertraline/Fluconazole Antifungal Activity and Minimize Drug Side Effect in Cryptococcus meningitis

Development of drug resistance in Cryptococcus meningitis (C. neoformans), which causes around 1 million symptomatic infections yearly, have an overwhelming impact on human health. Up to 60% of meningitis patients experienced relapse due to drug resistance that were linked mostly to Fluconazole resistance. The limited array of antifungal drugs and the global resistance in C. neoformans vindicates the need to develop new therapeutic approaches. The objective of this research is to utilize a Halal alternative formulation that maximizes the drug bioavailability and minimizes drug toxicity and resistance to C. neoformans. Different nanoemulsion (NE) formulations were prepared using clove oil, sertraline and fluconazole and their antifungal effect were tested individually and in combination as a mixture. Particle size and polydispersity index determination (PDI) of the prepared NEs were measured utilizing Dynamic light scattering technique and Zetatrac Particle size analyzer. In vitro antifungal evaluation was applied to assess the sensitivity of the developed NEs using agar diffusion technique. The tested NEs showed nanometric size with PDI ranging from 0.281 to 0.493 indicating homogenously dispersed systems. Moreover, the developed NEs elicited stronger zone of inhibition compared to same drugs suspended in water. As NEs formulation showed greater antifungal inhibition zone compared to traditional formulation, these findings can be utilized to produce a Halal potent antifungal drug with minimal inhibitory concentration that generate the maximum effect.