An FbD directed fabrication and investigation of luliconazole based SLN gel for amelioration of candida vulvovaginitis: 2T (thermosensitive & transvaginal) approach

Abstract Candidal vulvovaginitis (CVV), is the second most leading vaginal infection (global prevalence >75%), caused due to excessive growth of Candida spp., predominantly Candida albicans (>95% cases). The current treatment regimens for CVV are marred with the challenges of fungal resistance & infection recurrence, subsequently leading to the compromised therapeutic efficacy of anti-fungal drugs, prolonged treatment and low patient compliance. The core of the present research was the fabrication & investigation of 2T-SLN (solid lipid nanoparticles) gel carrying luliconazole for the amelioration of CVV. ‘2T’ symbolizes transvaginal & thermosensitive attributes of the present formulation. SLNs were prepared by a modified melt emulsification-ultra sonication method using a combination of solid lipids (Gelucire 50/13 & Precirol ATO5), surfactant (Tween 80) and co-surfactant (Kolliphor). Formulation by design (FbD) approach was adopted to obtain appropriately screened and tailored SLNs. The optimized SLNs yielded a particle size, polydispersity index & entrapment efficiency of 62.18 nm, 0.263 & 81.5% respectively. To formulate the 2T- gel, the final SLNs were loaded into Carbopol 971P-NF and Triethanolamine based gel. The 2T-SLN gel was found to be easily spreadable and homogenous with mean extrudability (15±0.4g/cm2), viscosity (696.42±2.34Pa·s) and %drug content (93.24±0.73%) values.. The pH of the prepared 2T-SLN gel (4.5 ±0.5) was in concordance with the vaginal pH (normal conditions). For in-vitro characterization of an optimized 2T-SLN gel the release kinetics & anticandidal activity were assessed which offers a %cumulative drug release of 62±0.5% in 72h and 37.3±1.5mm zone of inhibition in 48h. The visual appearance & dimensions were determined using fluorescent microscopy (spherical shape) & transmission electron microscopy (90- 120 nm) respectively. The optimized 2T-SLN gel showcases a skin-friendly profile with no significant signs of erythema and oedema and was found to be stable at room temperature for 2 months without any visual non-uniformity/cracking/breaking. In conclusion, the current research serves a new therapeutic perspective in assessing the activity of luliconazole for vaginal drug delivery using a 2T-SLN gel system.