Fluconazole-loaded solid lipid nanoparticles (SLNs) as a potential carrier for buccal drug delivery of oral candidiasis treatment using the Box-Behnken design

Abstract

The purpose of the present examination was to prepare fluconazole (FZ)-loaded solid lipid nanoparticles (FZ-loaded SLNs) for a buccal drug delivery system using the Box-Behnken design. The FZ-loaded SLNs were prepared using hot homogenization via an ultrasonic probe. The solid lipid, stabilizer, and active ingredient were glyceryl monostearate (GMS) (X1), Tween 80® (X2), and FZ (X3), respectively. The particle size of the FZ-loaded SLNs was in the nano-range of 32.86–269.3 nm. The polydispersity index (PDI) showed a relatively narrow size distribution and was in the range of 0.254–0.495. The zeta potential of all formulations was negatively charged and ranged from −19.8 to −36.9 mV. The entrapment efficiency (%EE) was 56.69–85.49%. Transmission electron microscopy confirmed that the FZ-loaded SLNs were in the nano-range and were spherical. The absence of FZ's melting peak in differential scanning calorimetry thermograms of the FZ-loaded SLNs indicated that the drug had been wholly incorporated into the lipid matrix and had changed from crystalline to amorphous form. The absence of FZ's characteristic peaks in the FZ-loaded SLNs in the Fourier transform infrared spectra confirmed the complete incorporation of FZ in the SLN lipid matrix. The maximum of the determination coefficient (R2) of the Higuchi model was much higher than that of the other models, suggesting that the FZ's kinetic release profile was diffusion-controlled. Permeation studies using porcine buccal mucosa were performed, and at 12 h, the drug could be detected in the buccal tissue, including that in the receptor chamber. The in vitro antifungal activity of the selected FZ-loaded SLNs was studied against Candida albicans, and all selected FZ-loaded SLNs showed inhibition zones, indicating that the FZ from the FZ-loaded SLNs had an antifungal effect. Therefore, FZ-loaded SLNs is a promising drug delivery carrier for local and systemic treatment of candidiasis through the buccal mucosa.