Formulation of topical gel contains a novel benzoic acid derivative for skin infection treatment: in vitro and in vivo evaluations.

Abstract

Objective: The increasing prevalence of antimicrobial resistance and the adverse effects associated with systemic administration of antibiotics necessitate the development of alternative therapeutic strategies. The new benzoic acid derivative: (E)-2-(1-isobutyl-2-oxoindolin-3-ylideneamino)-4-chlorobenzoic acid (IOACA) was reported to have a potent activity against Gram-positive bacteria including S. aureus and B. subtilis. That significant activity of IOACA and its log P value of 1.66 prompted us to formulate IOACA as a topical gel for the treatment of skin infections.

Methods: Formulation of a topical gel using Carbopol 934 as gelling agent; physicochemical characterization including drug content, viscosity, spreadability, pH determination, in vitro release study, and release kinetics; in vitro assessment of the antimicrobial efficacy of the gel against Staphylococcus aureus and Bacillus subtilis by agar diffusion method; in vivo evaluation of skin irritation effect and antimicrobial activity of the gel using male albino rat model.

Results: The prepared gel showed homogeneity and consistency. The pH values range from 5.8 to 6.5, with good viscosity and spreadability. The drug content was in an acceptable range. The cumulative amount released of the drug ranged from (72.2 ± 1.3% to 107.6 ± 4.7%). F3 approaches zero-order kinetics. In vivo studies showed significant reduction in viable count and infection severity with complete curing of staphylococcal skin rat infection after eight days of treatment.

Conclusion: The novel benzoic acid derivative-based topical gel is a promising candidate for the treatment of skin infections, offering an effective alternative to systemic antibiotics and contributing to avoid the antimicrobial resistance.