Department of Electronic Science and Technology, University of Science and Technology of China , Hefei 230027, China.
School of Engineering Science, University of Science and Technology of China , Hefei 230027, China.
Mol Pharm. 2017 Dec 4;14(12):4725-4733. doi: 10.1021/acs.molpharmaceut.7b00862. Epub 2017 Nov 14.
Artemether is one of the most effective drugs for the treatment of chloroquine-resistant and Plasmodium falciparum strains of malaria. However, its therapeutic potency is hindered by its poor bioavailability. To overcome this limitation, we have encapsulated artemether in poly(lactic-co-glycolic) acid (PLGA) core-shell microparticles (MPs) using the coaxial electrospray method. With optimized process parameters including liquid flow rates and applied electric voltages, experiments are systematically carried out to generate a stable cone-jet mode to produce artemether-loaded PLGA-MPs with an average size of 2 μm, an encapsulation efficiency of 78 ± 5.6%, and a loading efficiency of 11.7%. The in vitro release study demonstrates the sustained release of artemether from the core-shell structure in comparison with that of plain artemether and that of MPs produced by single-axial electrospray without any relevant cytotoxicity. The in vivo studies are performed to evaluate the pharmacokinetic characteristics of the artemether-loaded PLGA-MPs. Our study implies that artemether can be effectively encapsulated in a protective shell of PLGA for controlled release kinetics and enhanced oral bioavailability.
蒿甲醚是治疗抗氯喹和恶性疟原虫疟原虫菌株最有效的药物之一。然而，其生物利用度差限制了其治疗效果。为了克服这一限制，我们使用同轴电喷雾法将蒿甲醚包封在聚乳酸-共-羟基乙酸（PLGA）核壳微球（MPs）中。通过优化包括液体流速和施加电压在内的工艺参数，系统地进行实验以产生稳定的锥形射流模式，从而生成平均粒径为 2μm、包封效率为 78±5.6%、载药量为 11.7%的载药 PLGA-MPs。体外释放研究表明，与普通蒿甲醚和单轴电喷雾制备的无任何相关细胞毒性的 MPs 相比，芯-壳结构中能实现蒿甲醚的持续释放。体内研究用于评估载药 PLGA-MPs 的药代动力学特征。我们的研究表明，蒿甲醚可以有效地封装在 PLGA 的保护性外壳中，以实现控制释放动力学和提高口服生物利用度。
