Cited by 183Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsAdvanced Polymer Synthesis and Characterization

In vivo fate of unimers and micelles of a poly(ethylene glycol)-block-poly(caprolactone) copolymer in mice following intravenous administration

Liu, Jubo, Zeng, Faquan, Allen, Christine·2007·European Journal of Pharmaceutics and Biopharmaceutics

Abstract

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(5000)-b-PCL(5000) micelles were selected for further in vitro characterization and an in vivo evaluation of their fate and stability following intravenous (i.v.) administration. Specifically, (3)H-labelled MePEG(5000)-b-PCL(5000) 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 micelles, (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 CMC following distribution. Analysis of plasma samples from this group revealed that even 24 h post-administration 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.

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Crossref · 10.1016/j.ejpb.2006.11.010

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Authors
Liu, J., Zeng, F., & Allen, C.
Affiliations
University of Toronto (CA)
Corresponding author
Allen, Christine
Venue
European Journal of Pharmaceutics and Biopharmaceutics
Publisher
Elsevier BV
Published
2007-03
Volume
65
Issue
3
Pages
309-319
ISSN
0939-6411 (ISSN-L)
OpenAlex
W1986339830
Cited by
183
References
32
Citations by year
2026: 1 · 2025: 2 · 2023: 8 · 2022: 7 · 2021: 7 · 2020: 11 · 2019: 9 · 2018: 2 · 2017: 10 · 2016: 12 · 2015: 8 · 2014: 18 · 2013: 9 · 2012: 16
FWCI
4.96
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Pharmaceutics and Biopharmaceutics (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council of Canada
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Chemistry › Organic Chemistry › Advanced Polymer Synthesis and Characterization
Keywords
micelles, intravenous administration, tissue distribution, circulation half-life, micelle stability, critical micelle concentration, cationic ring-opening polymerization, plasma protein binding
MeSH terms
Animals, Biocompatible Materials, Drug Carriers, Half-Life, Injections, Intravenous, Kidney, Liver, Lung, Mice, Inbred BALB C, Micelles, Myocardium, Polyesters, Polyethylene Glycols, Protein Binding, Spleen, Thermodynamics, Tissue Distribution, Tritium, Mice, Nanoparticles

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