In vivo fate of unimers and micelles of a poly(ethylene glycol)-block-poly(caprolactone) copolymer in mice following intravenous administration
In vivo fate of unimers and micelles of a poly(ethylene glycol)-block-poly(caprolactone) copolymer in mice following intravenous administration
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DOI：
10.1016/j.ejpb.2006.11.010
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发表时间：
2007-03-01
影响因子：
4.9
通讯作者：
Allen, Christine
中科院分区：
文献类型：
--
作者：
Liu, Jubo;Zeng, Faquan;Allen, Christine
采用阳离子开环聚合法合成了不同PEG嵌段长度和相同PCL嵌段长度的甲氧基聚乙二醇-b-聚己内酯（MePEG-b-PCL）共聚物，并将其用于形成纳米胶束。由于其小尺寸和上级体外稳定性，选择MePEG（500）-b-PCL 5000胶束用于进一步体外表征和在静脉内（i. v.）局具体地，将H-3-标记的MePEG（5000）-b-PCL 5000胶束以250、2和0.2mg/kg的共聚物剂量静脉内施用给Balb/C小鼠，以分别检查（1）组装为药物稳定胶束的共聚物、（2）组装为药物不稳定胶束的共聚物和（3）共聚物单聚体的分布动力学。总体而言，发现当共聚物组装成化学稳定的胶束时，材料有效地限制在血浆隔室中。有趣的是，发现该共聚物具有相对长的循环半衰期，即使当以在分布后可能降至低于CNIC的浓度的剂量施用时。来自该组的血浆样品的分析显示，即使在给药后24小时，共聚物的显著部分仍然组装为完整的胶束。以这种方式，该研究证明PCL核的疏水性和半结晶性质赋予该胶束体系高度的动力学稳定性。(c)2006 Elsevier B. V.保留所有权利。
Methoxy poly(ethylene glycol)-b-poly(caprolactone) (MePEG-b-PCL) copolymers with varying PEG block lengths and a constant PCL block length were synthesized by cationic ring-opening polymerization and used to form nano-sized micelles. Due to their small size and superior in vitro stability, the MePEG(500)-b-PCL5000 micelles were selected for further in vitro characterization and an in vivo evaluation of their fate and stability following intravenous (i.v.) administration. Specifically, H-3-labelled MePEG(5000)-b-PCL5000 micelles were i.v. administered to Balb/C mice at copolymer doses of 250, 2 and 0.2 mg/kg in order to examine the distribution kinetics of (1) copolymer assembled as thermodynamically stable rnicelles, (2) copolymer assembled as thermodynamically unstable micelles and (3) copolymer unimers, respectively. Overall, it was found that when the copolymer is assembled as thermodynamically stable micelles the material is effectively restricted to the plasma compartment. Interestingly, the copolymer was found to have a relatively long circulation half-life even when administered at a dose that would likely fall to concentrations below the CNIC following distribution. Analysis of plasma samples from this group revealed that even 24 h post-achninistration a significant portion of the copolymer remained assembled as intact micelles. In this way, this study demonstrates that the hydrophobic and semi -crystalline nature of the PCL core imparts a high degree of kinetic stability to this micelle system. (c) 2006 Elsevier B.V. All rights reserved.