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Purpose. To assess the improvement in oral bioavailability and efficacy in systemic candidiasis treatment of miconazole nitrate (MN) formulations in murine models of candidiasis. Methods. Selected formulations containing 5% of  Softisan + Phospholipon 90H lipid matrix with 3% of MN ( A 1 ), 5% of  stearic   acid + Phospholipon 90H lipid matrix with 3% of MN ( B 1 ), and 5%  Softisan + stearic   acid + Phospholipon 90H with 3% of MN ( C 1 ) from the in vitro investigation were used for the study. Their acute toxicity was assessed using Lorke’s method (with slight modification) while bioavailability was determined using the bioassay method. The optimized batch ( A 1 ) was tested in murine systemic candidiasis induced in cyclophosphamide-immunosuppressed mice. The mice were treated with a single oral dose (100 mg/kg) of the formulations for five days. Serum fungal counts (cfu/mL) were determined on days 1, 3, and 5 of the treatment period. Haematological assessments were done. Results. The lipid formulations were safer than MN powder with LD50 values of 3162.8 and 1118.3 mg/kg. Bioavailability determination revealed a higher area under the curve (AUC) value for formulations  A 1 (6.11 μg/hr/mL) and  B 1 (4.91 μg/hr/mL) while formulation  C 1 (1.80 μg/hr/mL) had a lower AUC than MN (4.46 μg/hr/mL). Fungi were completely cleared from the blood of animals treated with the optimized formulation by day 3 as opposed to the controls (MN and Tween® 20) which still had fungi on day 5. No significant increase ( p &gt; 0.05 ) in haematological parameters was observed in mice treated with  A 1 . Conclusion. Formulation  A 1 successfully cleared Candida albicans from the blood within a shorter period than miconazole powder. This research has shown the potential of orally administered MN-loaded SRMS-based microparticles in combating systemic candidaemia.

biomed research international

Solidified Reverse Micellar Solution- (SRMS-) Based Microparticles for Enhanced Oral Bioavailability and Systemic Antifungal Efficacy of Miconazole Nitrate in Immunocompromised Mice