Doxorubicin-loaded nanosized micelles of a star-shaped poly(ε- caprolactone)-polyphosphoester block co-polymer for treatment of human breast cancer

Nguyen Van Cuong, Ming Fa Hsieh*, Yung Tsung Chen, Ian Liau

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Star-shaped co-polymers based on the backbone of poly(ε-caprolactone) were synthesized by a ring-opening reaction using pentaerythritol as initiator and Sn(Oct)2 as catalyst. The star-shaped poly(ε-caprolactone) polymer was then chain extended with a terminal block of poly(ethyl ethylene phosphate) to form a copolymer, poly(ε-caprolactone)-poly(ethyl ethylene phosphate), when using the cyclic ethyl ethylene phosphate monomer. The amphiphilic block co-polymers can self-assemble into nanoscopic micelles with a mean diameter of 150 nm and a spherical shape. Additionally, the prepared micelles did not induce hemolysis and nitric oxide production in vitro based on nitric oxide, hemolytic tests and MTT assays. The hydrophobic micellar cores encapsulated doxorubicin (DOX) in an aqueous solution with a loading efficiency of 55.2%. The in vitro release of DOX from DOX-loaded micelles was pH dependent. DOX-loaded micelles present significantly enhanced cytotoxicity to both MCF-7/drug-sensitive and MCF-7/drug-resistant cells after second incubation. Moreover, results of confocal microscopy and flow cytometry of DOX-loaded micelles demonstrate the feasibility of this delivery system for effective therapy of drug-resistant tumours.

Original languageEnglish
Pages (from-to)1409-1426
Number of pages18
JournalJournal of Biomaterials Science, Polymer Edition
Volume22
Issue number11
DOIs
StatePublished - 29 Apr 2011

Keywords

  • doxorubicin
  • micelles
  • multidrug resistance
  • poly(ε-caprolactone)
  • poly(ethyl ethylene phosphate)
  • Star-shaped co-polymer

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