Molecular design of biodegradable polymeric micelles for temperature-responsive drug release

Masamichi Nakayama, Teruo Okano*, Takanari Miyazaki, Fukashi Kohori, Kiyotaka Sakai, Masayuki Yokoyama

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

327 Citations (Scopus)


We designed thermo-responsive and biodegradable polymeric micelles for an ideal drug delivery system whose target sites are where external stimuli selectively release drugs from the polymeric micelles. The thermo-responsive micelles formed from block copolymers that were composed both of a hydrophobic block and a thermo-responsive block. Poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) showing a lower critical solution temperature (LCST) around 40 °C was synthesized for the thermo-responsive block, while biodegradable poly(d,l-lactide), poly(ε-caprolactone), or poly(d,l-lactide-co-ε-caprolactone) was used for the hydrophobic block. By changing both the block lengths of the poly(d,l-lactide)-containing block copolymers, physical parameters such as micelle diameter and critical micelle concentration were varied. On the other hand, the choice of the hydrophobic block was revealed to be critical in relation to both on the thermo-responsive release of the incorporated anti-cancer drug, doxorubicin, and the temperature-dependent change of the hydrophobicity of the micelles' inner core. One polymeric micelle composition successfully exhibited rapid and thermo-responsive drug release while possessing a biodegradable character.

Original languageEnglish
Pages (from-to)46-56
Number of pages11
JournalJournal of Controlled Release
Issue number1
Publication statusPublished - 2006 Sept 28


  • Biodegradable polymer
  • Polymeric micelle
  • Targeting
  • Temperature
  • Thermo-response

ASJC Scopus subject areas

  • Pharmaceutical Science


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