Design, Optimization, And Evaluation of Terbinafine-Loaded Nanogel for Enhanced Transungual Delivery and Antifungal Efficacy Against Onychomycosis

Abstract

The present study focuses on the design, optimization, and evaluation of terbinafine-loaded nanogel aimed at enhancing transungual drug delivery and antifungal efficacy against onychomycosis. Pre-formulation studies confirmed terbinafine’s higher solubility in propylene glycol and compatibility with selected excipients through FTIR and DSC analyses. The nanogel was prepared using an emulsification–ionic gelation method and optimized via a Quality by Design (QbD) approach. Characterization studies revealed a mean particle size of ~118 nm, narrow PDI (0.21), and a zeta potential of −28 mV, indicating good stability. TEM imaging confirmed spherical nanoparticles in the range of 36–43 nm. The optimized formulation demonstrated shear-thinning rheology, pH within the physiological range (5.6), high drug content uniformity (~98%), and entrapment efficiency (>90%). In vitro drug release studies using dialysis and Franz diffusion cells showed sustained release (>90% at 24 h), following Higuchi kinetics with anomalous transport mechanism. Nail penetration studies confirmed a ~3-fold increase in drug flux and ~3-fold higher drug retention in nail plates compared to pure terbinafine suspension. Antifungal activity assessments revealed significantly lower MIC and MFC values for the nanogel (0.25–0.5 μg/ml) compared to suspension (1–2 μg/ml), along with larger inhibition zones (32 mm vs. 21 mm against T. rubrum). Time-kill assays further confirmed rapid fungicidal action, achieving complete kill within 24 h for nanogel, whereas suspension required up to 48 h. These findings demonstrate that terbinafine-loaded nanogel provides enhanced solubility, sustained release, improved transungual penetration, and superior antifungal efficacy compared to conventional formulations. This nanogel system holds promise as a potential topical therapeutic approach for effective and patient-compliant management of onychomycosis.