Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research, 1 Pesek Road, Jurong Island, Singapore 627833, Singapore.
Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Int J Mol Sci. 2021 Jan 24;22(3):1141. 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.
蒿甲醚是青蒿素的衍生物，用于治疗危及生命的严重疟疾。本研究旨在利用纳米技术开发蒿甲醚的静脉注射剂型。采用改良的抗溶剂沉淀法，以酪蛋白酸钠作为稳定剂制备载蒿甲醚的玉米醇溶蛋白纳米粒。随后对纳米粒的理化性质进行了表征；用红细胞考察了其体外溶血性质，并用 Sprague-Dawley 大鼠考察了静脉给药后的药代动力学特征。结果表明，载蒿甲醚玉米醇溶蛋白纳米粒具有良好的包封效率、优异的物理稳定性，并具有体外缓释性能。有趣的是，将蒿甲醚包封于玉米醇溶蛋白纳米粒中可显著抑制溶血，这是青蒿素类抗疟药物治疗后常见的临床现象。与游离蒿甲醚制剂相比，静脉给予载蒿甲醚玉米醇溶蛋白纳米粒可使蒿甲醚的平均驻留时间延长约 80%（82.9 ± 15.2 与 45.6 ± 16.4 min， < 0.01），提示纳米粒可能延长治疗持续时间并减少临床给药频率。总之，静脉给予载蒿甲醚玉米醇溶蛋白纳米粒似乎是治疗严重疟疾的一种很有前途的治疗选择。
