Cited by 139Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsDendrimers and Hyperbranched Polymers

Influence of serum protein on polycarbonate-based copolymer micelles as a delivery system for a hydrophobic anti-cancer agent

Liu, Jubo, Zeng, Faquan, Allen, Christine·2005·Journal of Controlled Release

Abstract

A new micelle system formed from methoxy (polyethylene glycol)-b-poly (5-benzyloxy-trimethylene carbonate; MePEG-b-PBTMC 5000-b-4800) was investigated as a delivery system for the hydrophobic anti-cancer agent, ellipticine. The ellipticine was loaded into the MePEG-b-PBTMC micelles with a loading efficiency of 95% using a high-pressure extrusion technique. The ellipticine-loaded micelles have a spherical morphology and an average diameter of 96 nm. The anti-cancer activity of ellipticine was confirmed to be retained following formulation in the MePEG-b-PBTMC micelles. The extent of protein adsorption to the MePEG-b-PBTMC micelles was investigated by transmission electron microscopy, dynamic light scattering and gel filtration chromatography. Overall, the amount of protein both loosely and tightly associated with the micelles was found to be minimal and insignificant. The partitioning properties of ellipticine between an aqueous medium containing protein and the MePEG-b-PBTMC micelles were examined over a range of protein concentrations. Under physiologically relevant conditions, it was found that 61% of the drug remained within the micelle fraction while 39% was in the protein-containing aqueous phase. In addition, the in vitro drug release profile of ellipticine from the micelles was fit using a modified Higuchi model and found to be accelerated in the presence of protein. These studies demonstrate that although there are no significant interactions between micelle and protein, the properties of the micelle as a delivery vehicle may be strongly influenced by protein-drug interactions.

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Crossref · 10.1016/j.jconrel.2004.12.013

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Authors
Liu, J., Zeng, F., & Allen, C.
Affiliations
University of Toronto (CA)
Corresponding author
Allen, Christine
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2005-03
Volume
103
Issue
2
Pages
481-497
ISSN
0168-3659 (ISSN-L)
OpenAlex
W2002182083
Cited by
139
References
54
Citations by year
2025: 2 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 2 · 2019: 5 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 10 · 2014: 9 · 2013: 8 · 2012: 11
FWCI
4.76
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Controlled Release (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Natural Sciences and Engineering Research Council of Canada
  • National Cancer Institute
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords
ellipticine, polymeric micelles, protein adsorption, serum proteins, drug-protein interactions, anticancer drug delivery, high-pressure extrusion, drug loading efficiency, drug release kinetics, Higuchi model
MeSH terms
Antineoplastic Agents, Blood Proteins, Cell Survival, Drug Carriers, Drug Compounding, Ellipticines, Humans, Kinetics, Micelles, Models, Chemical, Particle Size, Polyethylene Glycols, Solubility, Cell Line, Tumor

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