In vivo antimalarial activity and pharmacokinetics of artelinic acid-choline derivative liposomes in rodents

被引：16

作者：

Duan, Shuai ^{[1
]}

Wang, Ruili ^{[1
]}

Wang, Rongrong ^{[1
]}

Tang, Jiaqi ^{[1
]}

Xiao, Xiaoyang ^{[1
]}

Li, Ning ^{[1
]}

Guo, Wenju ^{[1
]}

Yang, Qingshan ^{[1
]}

Ren, Guolian ^{[1
]}

Zhang, Shuqiu ^{[1
]}

机构：

[1] Shanxi Med Univ, Sch Pharm, 56 Xinjian South Rd, Taiyuan 030001, Shanxi, Peoples R China

来源：

PARASITOLOGY | 2020年 / 147卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Antimalaria; artelinic acid; choline derivative; pharmacokinetics;

D O I：

10.1017/S0031182019001306

中图分类号：

R38 [医学寄生虫学]; Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ; 100103 ;

摘要：

It is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method. Efficacy of ADLs was evaluated by Peters 4-day suppression test. The suppression percentage against Plasmodium yoelii BY265 (PyBY265) in ADLs group was higher than those of positive control groups (dihydroartemisinin liposomes, P < 0.05) and other control groups (P <= 0.05) at the doses of 4.4, 8.8, 17.6 mu mol (kg center dot d)(-1), respectively. The negative conversion fraction, recrudescence fraction and survival fraction of ADLs group were superior to other control groups. Pharmacokinetics in rats after intravenous injection suggested that ADLs exhibited higher exposure levels (indexed by area under concentration-time curve) than that of AD solution, artelinic acid liposomes or artelinic acid solution (P < 0.01). Taken together, ADLs exhibited promising antimalarial efficacy and pharmacokinetic characteristics.

引用

页码：58 / 64

页数：7

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