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Preparation of core cross-linked PCL-PEG-PCL micelles for doxorubicin delivery in vitro.

Abstract
Doxorubicin has been widely used in cancer treatment, but its severe side-effects restrict its clinical application greatly. So, we hope to design a novel delivery system to decrease its side-effects. In this paper, we prepared core cross-linked micelle based on poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (CCPCEC) at about 30 nm in diameter with a narrow distribution. The prepared core cross-linked PCL-PEG-PCL micelles were employed to load doxorubicin by pH-induced self-assembly method. Doxorubicin-loading did not obviously affect the micelle size or size distribution. Furthermore, these micelles exhibited a significantly enhanced thermodynamic stability against dilution with aqueous solvents and showed CMC in the range of 1 x 10(-3) to 2 x 10(-3) mg/mL. Cytotoxicity study confirmed great biocompatibility of the micelles and showed that the encapsulated doxorubicin in CCPCEC micelles enhanced the cytotoxicity of doxorubicin on C26 cell line in vitro. Moreover, in vitro release profile demonstrated a significant difference between rapid release of free doxorubicin and much slower and sustained release of doxorubicin-loaded core cross-linked micelles. In addition, a faster DOX-release from micelles at pH 5.5 than that at pH 7.4 was also observed. These results suggested that this new biodegradable Core Cross-linked PCL-PEG-PCL Micelles might be potential carriers for drug delivery in cancer chemotherapy.
AuthorsJuan Zhang, Ke Men, Yingchun Gu, Xiuhong Wang, Maling Gou, Gang Guo, Feng Luo, Zhiyong Qian
JournalJournal of nanoscience and nanotechnology (J Nanosci Nanotechnol) Vol. 11 Issue 6 Pg. 5054-61 (Jun 2011) ISSN: 1533-4880 [Print] United States
PMID21770143 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibiotics, Antineoplastic
  • Micelles
  • Polyesters
  • poly(epsilon-caprolactone)-b-poly(ethyleneglycol)-b-poly(epsilon-caprolactone)
  • Polyethylene Glycols
  • Doxorubicin
Topics
  • Animals
  • Antibiotics, Antineoplastic (administration & dosage, chemistry, pharmacokinetics)
  • Cell Line, Tumor
  • Cell Survival
  • Doxorubicin (administration & dosage, chemistry, pharmacokinetics)
  • Drug Delivery Systems (methods)
  • Drug Stability
  • HEK293 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Mice
  • Micelles
  • Microscopy, Electron, Transmission
  • Nanoparticles (chemistry, ultrastructure)
  • Nuclear Magnetic Resonance, Biomolecular
  • Particle Size
  • Polyesters (administration & dosage, chemistry, pharmacokinetics)
  • Polyethylene Glycols (administration & dosage, chemistry, pharmacokinetics)
  • Spectrometry, Fluorescence

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