Influence of serum protein on polycarbonate-based copolymer micelles as a delivery system for a hydrophobic anti-cancer agent
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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PEG-b-PEYM micelles release drug triggered by acidic pH due to the presence of acid-labile ortho ester side-chains in the polymer.
“Similar results were obtained using PEG-b-PEYM (poly(ethylene glycol)-block-polymethacrylate) micelles: drug release is triggered by acidic pH, due to the presence of acidlabile ortho ester side-chains in the polymer (Fig. 5C) [126].”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [126]
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- Authors
- Liu, J., Zeng, F., & Allen, C.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Allen, Christine
- ORCID
- 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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