Formulation Development of Extract as Nanosuppository to Improve its Intrarectal Delivery for the Treatment of Malaria.

Background: Previous folkloric and experimental reports have demonstrated the antimalarial efficacy of Azadirachta indica (AZA) extracts. However, one of the major challenges facing its application for the clinical treatment of malaria is the design of an acceptable dosage form.

Objective: Consequently, we developed AZA extract-loaded nanostructured lipid carriers (NLC) for the formulation of suppositories, denoted as nanosuppositories, for intrarectal treatment of malaria.

Methods: Various batches of NLC-bearing AZA extract were formulated based on lipid matrices prepared using graded concentrations of Softisan®154 and Tetracarpidium conophorum or walnut oil. NLC was investigated by size and differential scanning calorimetry (DSC). Suppository bearing AZA extract-loaded NLC was developed using cocoa butter or theobroma oil, and their physicochemical properties were profiled. In vitro drug release and in vivo antimalarial activity (using Plasmodium berghei-infected mice) were investigated.

Results: NLCs exhibited sizes in nanometers ranging from 329.5 - 806.0 nm, and were amorphized as shown by DSC thermograms. Nanosuppositories were torpedo- or bullet- shaped, weighing 138 - 368 mg, softened/liquefied between 4.10 - 6.92 min, and had controlled release behaviour. In vivo antimalarial study revealed excellent antimalarial efficacy of the nanosuppositories comparable with a commercial brand (Plasmotrim®) and better than the placebo (unloaded nanosuppository), and without toxic alterations of hepatic and renal biochemical factors.

Conclusion: Thus, AZA extract could be rationally loaded in nanostructured lipid carriers (NLC) for further development as nanosuppository and deployed as an effective alternative with optimum convenience for intrarectal treatment of malaria.