Development of vardenafil hydrochloride-loaded silica nanoparticles with enhanced transdermal delivery

Abstract

The aim of the present study was to develop a promising silica nanoparticle system to enhance the transdermal delivery of vardenafil hydrochloride (VRD) for treatment of erectile dysfunction. VRD-loaded silica nanoparticles were prepared using chitosan, polyethylene glycol and tetraethyl orthosilicate. The systems were monitored for vesicle size, zeta potential, drug entrapment efficiency, permeation of the drug after 0.5 hour (Q0.5h) and after 12 hours (Q12h). The utmost achieved system (VRD-SNP5) was histopathologically examined for skin irritation, and evaluated via confocal laser scanning microscopy (CLSM). VRD-SNP5 system and an oral aqueous drug dispersion were used to determine VRD pharmacokinetic parameters using physiologically based pharmacokinetic (PBPK) modeling. The VRD-SNP5 system comprised spherical vesicles (440.50 nm) possessing high zeta potential (26.00 mV), promising EE percent (71.5%), low Q0.5h (39.5±2.6%), and high Q12h (91.5±4.5%). It exhibited modest histopathologic alterations in rat skin after a 12-hour leave-on period. CLSM revealed deep drug penetration via rat skin. Following the transdermal application of the VRD-SNP5 system, PBPK modeling proposed the achievement of lower Cmax values, delayed Tmax estimates, and higher AUC0-24h folds in adults (3 folds) and geriatrics (1.65 folds). It could be concluded that silica nanoparticles could represent a potential transdermal delivery system for VRD.