Repositioning miconazole nitrate for malaria: Formulation of sustained release nanostructured lipid carriers, structure characterization and in vivo antimalarial evaluation

• Published in: Journal of drug delivery science and technology 2021-02, Vol.61, p.102125, Article 102125
• Main Authors: Umeyor, Chukwuebuka Emmanuel, Okoye, Ifunanya, Uronnachi, Emmanuel, Okeke, Tochukwu, Kenechukwu, Franklin, Attama, Anthony
• Format: Article
• Language: English
• Subjects: Malaria; Miconazole; Nanostructured lipid carriers; Plasmodium berghei; Repurposing
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2020.102125

It has been previously claimed that miconazole (MNZ) has activity against Plasmodium falciparum in vitro. Therefore, this study aims to evaluate the potential of MNZ as an alternative antimalarial agent. MNZ was entrapped in nanostructured lipid carriers (NLC) based on Softisan®154 and soybean oil admixtures. Batches of MNZ-loaded NLC were characterized for particle size and surface charge, differential scanning calorimetry (DSC), x-ray diffractometry (XRD), and encapsulation efficiency (EE%). In vitro release and in vivo antimalarial evaluations (using a murine model) were also carried out. Particle size of NLC ranged from 175 to 525 nm, and surface charge from −20 to −27 mV. DSC thermograms showed amorphization of MNZ at low melting points and enthalpies. X-ray diffractograms showed broader and weaker patterns with few characteristic peaks of MNZ, and high EE% of 90–98% were recorded. In vitro release study showed controlled release effect with about 82% of MNZ released after 8 h. In vivo clearance of parasitaemia was drug loading-dependent and compared favourably with the positive control. Stability testing of the MNZ-loaded NLC exhibited no significant (p > 0.05) changes in EE% compared to initial analysis. Thus, MNZ could be repurposed as an effective alternative for the treatment of malaria. [Display omitted] •NLC based on Softisan® 154 and soybean oil had desirable physical properties.•NLC improved aqueous solubility and gastrostability of miconazole (MNZ).•MNZ-NLCs had sustained release and cleared Plasmodium berghei in vivo.•MNZ could be repurposed for the treatment of malaria.