Nasal Gel Loaded with Amphotericin Nanotransferosomes as Antifungal Treatment for Fungal Sinusitis.

Khaled M Hosny,Nabil A Alhakamy

doi:10.3390/pharmaceutics13010035

Abstract

On the basis of fungal involvement, rhinosinusitis is categorized into allergic, mycetoma, chronic, and acute invasive types. The aim of the current study was to evaluate the efficacy of an amphotericin gel in situ loaded with nanotransferosomes against Aspergillus flavus, which causes allergic rhinosinusitis. A Box–Behnken design was utilized to study the interaction among the nanotransferosomes and optimize independent variables in formulating them, in order to match the prerequisites of selected responses. The optimal formulation was determined to be 300 mg/mL soybean lecithin, 200 mg/mL amphotericin B (AMP), and 150 mg/mL clove oil, resulting in a particle size of 155.09 nm, 84.30% entrapment efficacy (EE), inhibition zone of 16.0 mm, and 0.1197 mmol serum creatinine. The optimized batch was further prepared into an in situ gel and evaluated for various parameters. The optimized formulation released 79.25% AMP and enhanced permeation through the nasal membrane, while the other formulations did not achieve complete absorption. According to in vivo tests using rabbits as animal models, the optimized AMP-nanotransferosomal formulations (NT) in in situ gel result in a non-significant difference among the various kidney function parameters. In conclusion, nasal in situ gel loaded with AMP-clove oil nanotreansfersomes can act as a promising novel carrier that enhances antifungal activity and decreases AMP nephrotoxicity.

Highlights

IntroductionAn escalating number of paranasal sinus fungal infections has been reported
In recent years, an escalating number of paranasal sinus fungal infections has been reported
The particle size of all trial batches was found to be in the range of 73 to 210 nm, and entrapment efficacy (EE) and inhibition zone were estimated in the range of

Summary

Introduction

An escalating number of paranasal sinus fungal infections has been reported. Amphotericin B (AMP) is a broad spectrum antibiotic that has been widely used to treat fungal infections (as a first-line management) and various leishmaniasis (as a second line management) [6,7]. Several nanoparticle formulations, including polymeric nanoparticles [8,9], nanocapsule [10], liposome [11], solid lipid nanoparticle [12,13] and micelles [14], have been developed to achieve the foresaid goals. Several commercial forms of AMP, such as micellar dispersion, liposomes, lipid-base formulation, have been been intensively researched. These systems suffer from dose-dependent toxicity [15], shortage of support for long-standing benefits [16,17], towering expenditure, and contradictory results

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Conclusion