Artemether-Loaded Zein Nanoparticles: An Innovative Intravenous Dosage Form for the Management of Severe Malaria

• Published in: International journal of molecular sciences Vol. 22; no. 3; p. 1141
• Main Authors: Boateng-Marfo, Yaa, Dong, Yuancai, Ng, Wai Kiong, Lin, Hai-Shu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.01.2021; MDPI
• Subjects: Administration, Intravenous; Animals; Antimalarials - administration & dosage; Antimalarials - therapeutic use; Artemether; Artemether - administration & dosage; Artemether - pharmacokinetics; Artemether - therapeutic use; Artemisinin; Caseins - chemistry; Delayed-Action Preparations; Encapsulation; Erythrocytes; Ethanol; extended release; hemolysis; intravenous; Intravenous administration; Malaria; Malaria - drug therapy; Nanoparticles; Nanoparticles - chemistry; Nanotechnology; Oxidation; Particle size; Physicochemical properties; Rats; Rats, Sprague-Dawley; Sodium; Tropical diseases; Zein; Zein - chemistry; artemisinin; intravenous; nanoparticles; severe malaria; sodium caseinate; pharmacokinetics; zein; artemether; extended release; hemolysis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22031141

Artemether, an artemisinin derivative, is used in the management of life-threatening severe malaria. This study aimed to develop an intravenous dosage form of artemether using nanotechnology. Artemether-loaded zein nanoparticles were prepared by modified antisolvent precipitation using sodium caseinate as a stabilizer. Subsequently, the physicochemical properties of the nanoparticles were characterized; the in vitro hemolytic property was examined with red blood cells, while the pharmacokinetic profile was evaluated in Sprague-Dawley rats after intravenous administration. The artemether-loaded zein nanoparticles were found to display good encapsulation efficiency, excellent physical stability and offer an in vitro extended-release property. Interestingly, encapsulation of artemether into zein nanoparticles substantially suppressed hemolysis, a common clinical phenomenon occurring after artemisinin-based antimalarial therapy. Upon intravenous administration, artemether-loaded zein nanoparticles extended the mean residence time of artemether by ~80% in comparison to the free artemether formulation (82.9 ± 15.2 versus 45.6 ± 16.4 min, < 0.01), suggesting that the nanoparticles may prolong the therapeutic duration and reduce the dosing frequency in a clinical setting. In conclusion, intravenous delivery of artemether by artemether-loaded zein nanoparticles appears to be a promising therapeutic option for severe malaria.