不同粒径辅酶Q_(10)乳剂和脂质体小鼠药物动力学和组织分布

目的研究不同粒径辅酶Q10乳剂和脂质体小鼠药物动力学和组织分布。方法以市售辅酶Q10注射液(S)为对照,考察其60 nm乳剂(E60)、120 nm乳剂(E120)、60 nm脂质体(L60)和120nm脂质体(L120)小鼠尾静脉给药后的药物动力学及组织分布特征;采用DAS2.1.1药物动力学软件,进行房室模型和统计矩两种模式拟合;以组织相对摄取率(re)为指标,评价载体的粒径和种类对组织靶向性的影响。结果不同粒径辅酶Q10乳剂和脂质体体内分布均符合双隔室模型;E60、E120、L60和L120的统计矩AUC分别是S组的1.17、1.50、5.99和8.65倍;re结果显示,E60组在心、脾和脑的含量分别是S组的2.64、2.74和1.95倍,E120组在心、脾和脑的含量分别是S组的4.89、3.77和2.38倍;L60组在脑中的含量是S组的1.56倍,L120组在脑和肺的含量分布是S组的2.28和1.85倍。结论载体粒径和种类对辅酶Q10体内分布的影响十分明显,市售注射液组、乳剂组和脂质体组的AUC依次增大,且同一载体中,120 nm组较60 nm组的AUC高;相对市售注射液,乳剂组对心、脾和脑有一定的靶向性,而脂质体组主要靶向于脑和肺,同一载体内,120 nm组在多数组织的富集量多于60 nm组。

Pharmacokinetics and tissue distribution of different particle sizes of CoQ10 emulsion and CoQ10 liposome in mice

Objective To study the pharmacokinetics and tissue distribution of CoQ₁₀ emulsions and CoQ₁₀ liposomes with different particle sizes in mice. Methods The commercial CoQ₁₀ injection was used as a reference to investigate the pharmacokinetics and tissue distribution of CoQ₁₀ emulsions and liposomes with different particle sizes given intravenous injection. All data were analyzed with compartment model and statistical moment respectively, using DAS software. Furthermore, the relative tissue exposure values (r_e) were utilized as an indicator to evaluate the effect of particle sizes and the type of carriers on the tissue targeting. Results The pharmacokinetic processes of CoQ₁₀ emulsions and CoQ₁₀ liposomes conformed to two compartmental models. The AUC calculated by statistical moment of E60, E120, L60, L120 was 1.17, 1.50, 5.99 and 8.65 times of the control group respectively. The r_e of E60 group in heart, spleen and brain was 2.64, 2.74 and 1.95 times over that of S group, but E120 group was 4.89, 3.77 and 2.38 respectively. The level of L60 in brain was 1.56 times compared with S group, while the distributions of L120 in brain and lung were 2.28 and 1.85 times up on that of S group. Conclusions Particle sizes and types of carriers had a significant effect on the biodistribution of CoQ₁₀. In rank order for AUC we find the least from commercial injections, then the emulsions, and the greatest from liposomes. For the same carrier, the AUC of 120nm group was higher than 60nm group. Comparing with commercial injections, emulsions were targeted to heart, spleen and brain, while liposomes were brain and lung. Moreover, the retained levels of 120 nm groups in tissues were more than 60 nm for the same carrier.