三氧化二砷聚乳酸纳米粒的制备及在大鼠体内药动学  

Preparation and Pharmacokinetics of Arsenic Trioxide-Loaded Polylactic Acid Nanoparticles in Rats

作　　者：王琪[1] 耿雪[1] 徐世一 苏慧[1] 李雪莹[1] 郝若祎 霍元子[1] 阎雪莹[1] WANG Qi;GENG Xue;XU Shiyi;SU Hui;LI Xueying;HAO Ruoyi;HUO Yuanzi;YAN Xueying(Heilongjiang University of Chinese Medicine, Harbin 150040, China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040

出　　处：《中医药信息》2021年第2期24-30,共7页Information on Traditional Chinese Medicine

基　　金：黑龙江省自然科学基金项目(LH2020H096)。

摘　　要：目的:制备As2O3纳米粒(As2O3-PLA-NPs、As2O3-mPEG-PLA-NPs),并考察其在大鼠体内吸收生物利用度。方法:采用复乳溶剂挥发法制备三氧化二砷纳米粒(As2O3-PLA-NPs、As2O3-mPEG-PLA-NPs),表征其外观形态、粒径、Zeta电位,并检测包封率、载药量及体外释放度。SD大鼠分别尾静脉注射As2O3生理盐水溶液和As2O3-PLA-NPs、AS2O3-mPEG-PLA-NPs注射液,比较药动学行为及生物利用度。结果:As2O3-PLA-NPs和As2O3-mPEG-PLA-NPs外观均呈球形,大小相似,分散性良好;平均粒径分别为(133.20±5)nm、(123.40±6)nm,Zeta电位分别为-6.7 mV、-7.11 mV,包封率分别为(86.32±0.54)%、(91.75±0.38)%;两种纳米粒前2 h无突释,均具有一定缓释作用,在72 h累积释放百分率分别为(64.84±1.18)%和(69.15±1.43)%;As2O3-PLA-NPs组T1/2为As2O3生理盐水组的1.52倍,AUC为1.42倍,As2O3-mPEG-PLA-NPs体内长循环效果更显著,T1/2为As2O3生理盐水组的2.53倍,AUC为2.20倍;mPEG修饰纳米粒子组的T1/2相比于PLA纳米粒组,有显著提高(P<0.05)。结论:应用复乳溶剂挥发法成功制备As2O3-PLA-NPs、As2O3-mPEG-PLA-NPs,方法简单可行;mPEG修饰的纳米粒子在体外释放,体内药动学方面表现出更好的缓释效果。Objective:To prepare nanoparticles of As2O3(As2O3-PLA-NPs,As2O3-mPEG-PLA-NPs),and to study the effects on the bioavailability of As2O3 in rats.Methods:The As2O3 nanoparticles were prepared by double emulsion solvent evaporation method.Its appearance,particle size and Zeta potential were characterized,as well as encapsulation rate,drug loading and in vitro drug release were detected respectively.The pharmacokinetics and bioavailability were compared after tail vein injected with As2O3 saline solution,As2O3-PLA-NPs and As2O3-mPEG-PLA-NPs injection respectively.Results:Nanoparticles were the shape of spherical,similar in size and with good dispersion.The average particle size was(133.20±5)nm and(123.40±6)nm,the Zeta potential was-6.7 mV and-7.11 mV,and the entrapment efficiency was(86.32±0.54)%and(91.75±0.38)%,respectively.Both nanoparticles had no burst release in the first two hours,they both had a certain sustained release,whereas As2O3-PLA-NPs and As2O3-mPEG-PLA-NPs in 72 h cumulative release was(64.84±1.18)%and(69.15±1.43)%.Pharmacokinetic results showed that T1/2 of As2O3-PLA-NPs group was 1.52 times and AUC was 1.42 times than that of As2O3 saline group.In vivo long circulating of As2O3-mPEG-PLA-NPs was more significant,T1/2 was 2.53 times and AUC was 2.20 times than As2O3 saline group.T1/2 of mPEG modified nanoparticles group was significantly increased compared to that of the PLA nanoparticles group(P<0.05).Conclusion:By using double emulsion solvent evaporation method,As2O3-PLA-NPs and As2O3-mPEG-PLA-NPs were successfully prepared,the method was simple and feasible.In terms of in vitro release,pharmacokinetic aspects,mPEG modified nanoparticles showed better release effect.

关 键 词：三氧化二砷 聚乳酸 药动学行为 生物利用度 

分 类 号：R284[医药卫生—中药学]