Thermosensitive and biodegradable polymeric micelles for paclitaxel delivery
Abstract
The preparation, release and in vitro cytotoxicity of a novel polymeric micellar formulation of paclitaxel (PTX) were investigated. The micelles consisted of an AB block copolymer of poly(N-(2-hydroxypropyl) methacrylamide lactate) and poly(ethylene glycol) (pHPMAmDL-b-PEG). Taking advantage of the thermosensitivity of pHPMAmDL-b-PEG, the loading was done by simply mixing of a small volume of a concentrated PTX solution in ethanol and an aqueous polymer solution and subsequent heating of the resulting solution above the critical micelle temperature of the polymer. PTX could be almost quantitatively loaded in the micelles up to 2 mg/mL. By dynamic light scattering and cryo-transmission electron microscopy, it was shown that PTX-loaded micelles have a mean size around 60 nm with narrow size distribution. At pH 8.8 and 37 degrees C, PTX-loaded micelles destabilized within 10 h due to the hydrolysis of the lactic acid side group of the pHPMAmDL. Because the hydrolysis of the lactic acid side groups is first order in hydroxyl ion concentration, the micelles were stable for about 200 h at physiological conditions. The presence of serum proteins did not have an adverse effect on the stability of the micelles during at least 15 h. Interestingly, the dissolution kinetics of pHPMAmDL-b-PEG micelles was retarded by incorporation of PTX, indicating a strong interaction between PTX and the pHPMAmDL block. The PTX-loaded micelles showed a release of the incorporated 70% of PTX during 20 h at 37 degrees C and at pH 7.4. PTX-loaded pHPMAmDL-b-PEG micelles showed comparable in vitro cytotoxicity against B16F10 cells compared to the Taxol standard formulation containing Cremophor EL, while pHPMAmDL-b-PEG micelles without PTX were far less toxic than the Cremophor EL vehicle. Confocal laser-scanning microscopy (CLSM) and fluorescence activated cell sorting (FACS) analysis of fluorescently labelled micelles showed that pHPMAmDL-b-PEG micelles were internalized by the B16F10 cells. The present results suggest that pHPMAmDL-b-PEG block copolymer micelles are a promising delivery system for the parenteral administration of PTX.
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Standard TEM can have interesting application for the determination of the cellular fate of micelles labeled with heavy atoms such as gold or radioactive probes.
“standard TEM can have interesting application for the determination of the cellular fate of micelles labeled with heavy atoms such as gold [90,172] or radioactive probes [90].”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [172]
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- Authors
- Soga, O., van Nostrum, C. F., Fens, M., Rijcken, C. J. F., Schiffelers, R. M., Storm, G., & Hennink, W. E.
- Affiliations
- Utrecht University (NL)
- Corresponding author
- Hennink, Wim E.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 103
- Issue
- 2
- Pages
- 341-353
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2024862077
- Cited by
- 319
- References
- 50
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 7 · 2023: 7 · 2022: 2 · 2021: 7 · 2020: 13 · 2019: 13 · 2018: 11 · 2017: 17 · 2016: 21 · 2015: 23 · 2014: 15 · 2013: 23 · 2012: 21
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- 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
- paclitaxel, polymeric micelles, thermosensitive block copolymers, polyethylene glycol, biodegradable micelles, drug delivery, controlled release, micelle stability, cytotoxicity, B16F10 melanoma cells
- MeSH terms
- Animals, Antineoplastic Agents, Phytogenic, Biocompatible Materials, Cell Survival, Drug Carriers, Drug Compounding, Drug Stability, Micelles, Particle Size, Polyethylene Glycols, Polymethacrylic Acids, Solubility, Temperature, Paclitaxel, Lactic Acid, Cell Line, Tumor, Mice
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