Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity

Abstract

Background and objective: Miconazole is a broad-spectrum antifungal drug that has poor aqueous solubility (<1 µg/mL); as a result, a reduction in its therapeutic efficacy has been reported. The aim of this study was to formulate and evaluate miconazole-loaded solid lipid nanoparticles (MN-SLNs) for oral administration to find an innovative way to alleviate the disadvantages associated with commercially available capsules.

Methods: MN-SLNs were prepared by hot homogenization/ultrasonication. The solubility of miconazole in different solid lipids was measured. The effect of process variables, such as surfactant types, homogenization and ultrasonication times, and the charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release, antifungal activity against Candida albicans, and in vivo pharmacokinetics were studied in rabbits.

Results: The MN-SLN, consisting of 1.5% miconazole, 2% Precirol ATO5, 2.5% Cremophor RH40, 0.5% Lecinol, and 0.1% Dicetylphosphate, had an average diameter of 23 nm with a 90.2% entrapment efficiency. Furthermore, the formulation of MN-SLNs enhanced the antifungal activity compared with miconazole capsules. An in vivo pharmacokinetic study revealed that the bioavailability was enhanced by >2.5-fold.

Conclusion: MN-SLN was more efficient in the treatment of candidiasis with enhanced oral bioavailability and could be a promising carrier for the oral delivery of miconazole.

Keywords: Cremophor RH40; Precirol ATO5; antifungal activity; encapsulation; miconazole; solid lipid nanoparticles.

Figure 1

Hydrodynamic diameter measurements of different miconazole-loaded solid lipid nanoparticle formulations.

Figure 2

Zeta potential measurements of different miconazole-loaded solid lipid nanoparticle formulations.

Figure 3

In vitro release profile of miconazole from MN-SLNs and pure miconazole powder. Abbreviation: MN-SLNs, miconazole-loaded solid lipid nanoparticles.

Figure 4

Inhibition zones for different formulations of miconazole against Candida albicans. Abbreviations: MN-SLN, miconazole-loaded solid lipid nanoparticle; SLN, solid lipid nanoparticle.

Figure 5

Plasma concentration–time curve for miconazole after oral administration of MN-SLNs and marketed capsules to rabbits at a dose of 10 mg/kg. Abbreviations: MN, miconazole-loaded; MN-SLNs, miconazole-loaded solid lipid nanoparticles.