Silver Nanoparticles Loaded Pluronic Hydrogel of Terbinafine Hydrochloride for Treatment of Onychomycosis
摘要
Globally 90% of toenail infections and 50% of nail problems are caused by onychomycosis. In the present study, a temperature responsive pluronic-based hydrogel containing terbinafine and silver nanoparticles was developed to enhance the effectiveness of this formulation for treatment of onychomycosis. Silver nanoparticles were synthesized by chemical method and evaluated for particle size and zeta potential. In-situ gel formulation containing a combination of pluronic F127 and pluronic F68 was optimized via design of experiments considering gel strength and gelling temperature as dependent variables. The optimized gels were assessed for rheological behaviour, drug content, cytotoxicity study, and in-vitro diffusion study using an artificial membrane and across a human nail plate. Optimized terbinafine hydrocholoride gels with and without silver nanoparticles were compared for antimicrobial activities against S. aureus and E. Coli and antifungal activities against C. albicans. In-vitro transungual efficacy against nail fungal pathogens like Trichophyton rubrum and T. mentagrophytes was performed using nail clippings. Optimized hydrogel containing 22% of pluronic F127 and 6% of pluronic F68 showed strong gelling behaviour (gel strength = 1262.643 Pa) near body temperature (33.33 °C). Rheological studies suggested the viscoelastic behaviour of hydrogel with a sol-to-gel transition near body temperature. In vitro diffusion study using an artificial membrane showed sustained drug release for 12 h, while diffusion study across a human nail device confirmed prolonged drug release up to 7 days. Cytotoxicity study with IC50 values for AgNPs-TB hydrogel of 1775.3/0.1 g/mL suggested that the formulation is safe to use. Silver nanoparticles-containing hydrogel showed broad antimicrobial activity, and improved antifungal activity, against nail fungal pathogens compared to terbinafine alone. In-vitro transungual study showed adequate drug flux across the human nail device for effective inhibition of Trichophyton rubrum and Trichophyton mentagrophytes. The results demonstrated that terbinafine combined with silver nanoparticles in pluronic-based hydrogels enhanced the effectiveness of the formulation in managing onychomycosis.
Graphical Abstract