Title:Formulation Development of Azadirachta indica Extract as Nanosuppository
to Improve its Intrarectal Delivery for the Treatment of Malaria
Volume: 16
Issue: 3
Author(s): Tochukwu Chimdindu Okeke, Chukwuebuka Emmanuel Umeyor*, Ifeanyi Thaddeus Nzekwe, Immaculeta Chikamnele Umeyor, Ngozi Maryann Nebolisa, Emmanuel Maduabuchi Uronnachi, Calistus Dozie Nwakile, Chizoba Austinline Ekweogu, Omoirri Moses Aziakpono and Anthony Amaechi Attama
Affiliation:
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Nanomedicines
and Drug Delivery Research Group, Nnamdi Azikiwe University, Awka 422001, Anambra State, Nigeria
Keywords:
Azadirachta indica, Tetracarpidium conophorum, malaria, Plasmodium falciparum, nanostructured lipid carriers, nanosuppositories.
Abstract:
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.
