Pharmaceutics Division, Central Drug Research Institute, Lucknow 226031, India; Banasthali Vidyapeeth, Banasthali, Rajasthan 304022, India.
Pharmaceutics Division, Central Drug Research Institute, Lucknow 226031, India.
Colloids Surf B Biointerfaces. 2015 Feb 1;126:467-75. doi: 10.1016/j.colsurfb.2014.12.052. Epub 2015 Jan 7.
The present work is focused on the preparation of nanoemulsions (NEs) loaded with arteether (ART) for its enhanced efficacy against malaria parasites. ART-NEs have been prepared using high pressure homogenization (HPH) technique with the aim of improving its solubility and thus its bioavailability. ART-NEs were optimized in terms of pressure and number of cycles. Globule size and size distributions were chosen as quality parameters. The maximum drug loading was achieved up to 93 ± 7.4% with globule size 156 ± 10.2 nm and zeta potential of -23.3 ± 3.4 mV. The developed ART-NEs were found to be stable in terms of globule size and size distribution at different pH. The in vitro release profile of the ART-NEs showed 62% drug release within 12h. The percentage cell viability of blank NEs were within acceptable limits. A sensitive assay method for the determination of ART in rat plasma by liquid chromatography-mass spectrometry (LC-MS) was employed after oral administration of ART-NEs. The pharmacokinetic study showed significantly enhanced bioavailability of ART in ART-NE-V. The area under curve (AUC) of ART-NE-V was AUC0-t 1988.411 ± 119.66 h ng/ml which was significantly higher (p<0.05) than ART in ground nut oil (GNO) AUC0-t 671.852 ± 187.05 h ng/ml. The Cmax of ART-NE-V (1506 ± 161.22 ng/ml) was also significantly higher (p<0.05) than ART in GNO (175.2 ± 16.54 ng/ml) and ART given intramuscularly (IM) (278.05 ± 38.59 ng/ml). The ART-NE-V was having significantly high antimalarial efficacy and survival rate of mice giving 80% cure rate at 12.5 mg/kg for 5 days in comparison to 30% cure rate of ART in GNO at the same daily dose and it was also comparable to the 100% cure rate at 12.5 mg/kg for 5 days for ART given intramuscularly. In conclusion ART-NE can be a promising oral delivery system for ART.
本工作集中于制备负载青蒿琥酯（ART）的纳米乳（NE）以提高其对疟原虫的疗效。ART-NE 是通过高压匀质（HPH）技术制备的，目的是提高其溶解度，从而提高其生物利用度。ART-NE 是在压力和循环次数方面进行优化的。球粒大小和粒度分布被选为质量参数。最大载药量达到 93±7.4%，球粒大小为 156±10.2nm，Zeta 电位为-23.3±3.4mV。在不同 pH 值下，所制备的 ART-NE 在球粒大小和粒度分布方面均表现出稳定。ART-NE 的体外释放曲线显示 12 小时内释放 62%的药物。空白 NE 的细胞存活率在可接受的范围内。采用液质联用（LC-MS）法测定大鼠血浆中 ART 的灵敏测定方法，经口服给予 ART-NE 后进行。药代动力学研究表明，ART-NE-V 显著提高了 ART 的生物利用度。ART-NE-V 的 AUC0-t 为 1988.411±119.66 h ng/ml，明显高于 ART 在花生油（GNO）中的 AUC0-t 671.852±187.05 h ng/ml（p<0.05）。ART-NE-V 的 Cmax（1506±161.22ng/ml）也明显高于 ART 在 GNO（175.2±16.54ng/ml）和肌内注射（IM）（278.05±38.59ng/ml）中的 Cmax（p<0.05）。ART-NE-V 在 5 天内每天给予 12.5mg/kg 时具有显著的抗疟疗效和小鼠存活率，治愈率为 80%，而在相同的日剂量下，ART 在 GNO 中的治愈率为 30%，与肌内注射 12.5mg/kg 时的 100%治愈率相当。总之，ART-NE 可以成为一种有前途的 ART 口服给药系统。
