FORMULATION, CHARACTERISATION AND IN VITRO STUDIES OF PALM-BASED LIPID NANOPARTICLES FOR TOPICAL DELIVERY OF GRISEOFULVIN

Abstract

Griseofulvin is a fungistatic agent that is effective against dermatophytosis. Currently, griseofulvin is only available as oral preparation. Its poor and highly variable bioavailability, long duration of treatment, systemic side effects and drug interactions generate interest in developing a topical griseofulvin formulation. The aim of the present study was to prepare a topical lipid nanoparticle formulation for griseofulvin, using palm-based materials. The lipid nanoparticles produced using high pressure homogenisation method were characterised and investigated for their in vitro performance. Transmission electron microscopy study showed spherical nanoparticles with smooth surface. The optimum formulation has a mean particle size of 179.8 nm with polydispersity index of 0.306, and zeta potential of -27.9 mV. The loading of griseofulvin in lipid nanoparticles was 0.77%. Differential scanning calorimetry study confirmed that the griseofulvin loaded lipid nanoparticles were solid (at room temperature and skin temperature) and appeared in amorphous state. As compared with the control griseofulvin, the in vitro studies showed that the griseofulvin loaded lipid nanoparticles had comparable antifungal activity [Trichophyton rubrum (MIC 0.5 μg/mL) and Trichophyton mentagrophytes (MIC 0.25 μg/mL)], better safety profile in human keratinocyte cells [(HaCaT) (a four-fold reduction of the cytotoxicity against HaCaT; IC50 30 ± 2.37 μg/mL)], higher skin permeation (flux of 0.067 ± 0.003 μg/cm2/hr) as well as better skin targeting effect (retention of 14.9 ± 0.483 μg/cm2 of griseofulvin on the epidermis of the porcine). The study highlighted the potential of palm-based lipid nanoparticles as carrier for griseofulvin to enhance its antifungal activity via topical route. The optimum formulation was obtained using Formulation B which was prepared using lipid C (99% triglycerides), Tween 80 (with lipid to surfactant ratio of 2:1) and was homogenised at 1500 bar with 5 cycles.