Novel Intravaginal Drug Delivery System Based on Molecularly PEGylated Lipid Matrices for Improved Antifungal Activity of Miconazole Nitrate.

The aim of this study was to investigate the potential of microparticles based on biocompatible phytolipids [Softisan® 154 (SF) (hydrogenated palm oil) and super-refined sunseed oil (SO)] and polyethylene glycol- (PEG-) 4000 to improve intravaginal delivery of miconazole nitrate (MN) for effective treatment of vulvovaginal candidiasis (VVC). Lipid matrices (LMs) consisting of rational blends of SF and SO with or without PEG-4000 were prepared by fusion and characterized and employed to formulate MN-loaded solid lipid microparticles (SLMs) by melt-homogenization. The SLMs were characterized for physicochemical properties, anticandidal activity, and stability. Spherical discrete microparticles with good physicochemical properties and mean diameters suitable for vaginal drug delivery were obtained. Formulations based on SO:SF (1:9) and containing highest concentrations of PEG-4000 (4 %w/w) and MN (3.0 %w/w) were stable and gave highest encapsulation efficiency (83.05-87.75%) and inhibition zone diameter (25.87±0.94-26.33±0.94 mm) and significantly (p<0.05) faster and more powerful fungicidal activity regarding killing rate constant values (7.10 x 10-3-1.09 x 10-2 min-1) than commercial topical solution of MN (Fungusol®) (8.00 x 10-3 min-1) and pure MN sample (5.160 x 10-3 min-1). This study has shown that MN-loaded SLMs based on molecularly PEGylated lipid matrices could provide a better option to deal with VVC.

Novel solidified reverse micellar solution-based mucoadhesive nano lipid gels encapsulating miconazole nitrate-loaded nanoparticles for improved treatment of oropharyngeal candidiasis.

OBJECTIVE: To develop and evaluate solidified-reverse-micellar-solution (SRMS)-based oromucosal nano lipid gels for improved localised delivery of miconazole nitrate (MN). METHODS: Phospholipon® 90G and Softisan® 154 (3:7) were used to prepare SRMS by fusion. Solid lipid nanoparticles (SLNs, 0.25-1.0% w/w MN) formulated with the SRMS by high shear homogenisation were employed to prepare mucoadhesive nano lipid gels. Physicochemical characterisation, drug release in simulated salivary fluid (SSF) (pH 6.8) and anti-candidal activity were carried out. RESULTS: The SLNs were spherical nanoparticles, had mean size of 133.8 ± 6.4 to 393.2 ± 14.5 nm, low polydispersity indices, good encapsulation efficiency (EE) (51.96 ± 2.33-67.12 ± 1.65%) and drug loading (DL) (19.05 ± 2.44-24.93 ± 1.98%). The nano lipid gels were stable, spreadable, pseudoplastic viscoelastic mucoadhesive systems that exhibited better prolonged release and anti-candidal properties than marketed formulation (Daktarin® oral gel) (p < 0.05). CONCLUSION: This study has shown that SRMS-based nano lipid gels could be employed to prolong localised oromucosal delivery of MN.