학술논문
Murine pharmacokinetics and antimalarial pharmacodynamics of dihydroartemisinin trimer self-assembled nanoparticles
Helminthology - Original Paper
Helminthology - Original Paper
Document Type
Academic Journal
Author
Source
Parasitology Research. August 2021, Vol. 120 Issue 8, p2827, 11 p.
Subject
Language
English
ISSN
0932-0113
Abstract
Author(s): Wenju Guo [sup.1], Ning Li [sup.1], Guolian Ren [sup.1], RongRong Wang [sup.1], Liqing Chai [sup.1], Yujie Li [sup.1], Xi Wang [sup.1], Qingshan Yang [sup.1], Ruili Wang [sup.1], Guoshun Zhang [...]
Currently, conjugation of artemisinin-derived dimers, trimers, and tetramers is a viable strategy for developing new effective antimalarial candidates. Furthermore, nanotechnology is an effective means to achieve intravenous administration of hydrophobic drugs. In this paper, an ester-linked dihydroartemisinin trimer (DHA.sub.3) was synthesized and further prepared as self-assembled nanoparticles (DHA.sub.3NPs) by a one-step nanoprecipitation method. The pharmacokinetics and antimalarial pharmacodynamics of DHA.sub.3NPs were studied in rats and mice infected with Plasmodium yoelii BY265 (PyBY265). DHA.sub.3NPs had a regular spherical shape with a uniform size distribution of 140.27 ± 3.59 nm, entrapment efficiency (EE) of 99.63 ± 0.17%, and drug loading efficiency (DL) of 79.62 ± 0.11%. The in vitro release characterization revealed that DHA.sub.3NPs were easily hydrolysed into DHA in an esterase environment. The pharmacokinetics study demonstrated that the area under the concentration-time curve (AUC.sub.0-t) of DHA in DHA.sub.3NPs group was 2070.52 ± 578.76 hxngxmL.sup.-1, which was higher than that of DHA and artesunate (AS) control groups (AUC.sub.0-t values of 724.18 ± 94.32 and 448.40 ± 94.45 hxngxmL.sup.-1, respectively) (P < 0.05). The antimalarial pharmacodynamics in vivo suggested that DHA.sub.3NP.sub.S (ED.sub.90 7.82 ± 1.16 [mu]molx(kgxday).sup.-1) had a superior antimalarial effect compared with that of control groups (ED.sub.90 values of 14.68 ± 0.98 (DHA) and 14.34 ± 1.96 (AS) [mu]molx(kgxday).sup.-1) (P < 0.05). In addition, DHA.sub.3NP.sub.S reduced the recurrence ratio and improved the cure ratio and survival time. In summary, DHA.sub.3NPs exhibited promising pharmacokinetic characteristics and antimalarial pharmacodynamics in vivo.
Currently, conjugation of artemisinin-derived dimers, trimers, and tetramers is a viable strategy for developing new effective antimalarial candidates. Furthermore, nanotechnology is an effective means to achieve intravenous administration of hydrophobic drugs. In this paper, an ester-linked dihydroartemisinin trimer (DHA.sub.3) was synthesized and further prepared as self-assembled nanoparticles (DHA.sub.3NPs) by a one-step nanoprecipitation method. The pharmacokinetics and antimalarial pharmacodynamics of DHA.sub.3NPs were studied in rats and mice infected with Plasmodium yoelii BY265 (PyBY265). DHA.sub.3NPs had a regular spherical shape with a uniform size distribution of 140.27 ± 3.59 nm, entrapment efficiency (EE) of 99.63 ± 0.17%, and drug loading efficiency (DL) of 79.62 ± 0.11%. The in vitro release characterization revealed that DHA.sub.3NPs were easily hydrolysed into DHA in an esterase environment. The pharmacokinetics study demonstrated that the area under the concentration-time curve (AUC.sub.0-t) of DHA in DHA.sub.3NPs group was 2070.52 ± 578.76 hxngxmL.sup.-1, which was higher than that of DHA and artesunate (AS) control groups (AUC.sub.0-t values of 724.18 ± 94.32 and 448.40 ± 94.45 hxngxmL.sup.-1, respectively) (P < 0.05). The antimalarial pharmacodynamics in vivo suggested that DHA.sub.3NP.sub.S (ED.sub.90 7.82 ± 1.16 [mu]molx(kgxday).sup.-1) had a superior antimalarial effect compared with that of control groups (ED.sub.90 values of 14.68 ± 0.98 (DHA) and 14.34 ± 1.96 (AS) [mu]molx(kgxday).sup.-1) (P < 0.05). In addition, DHA.sub.3NP.sub.S reduced the recurrence ratio and improved the cure ratio and survival time. In summary, DHA.sub.3NPs exhibited promising pharmacokinetic characteristics and antimalarial pharmacodynamics in vivo.