Thermosensitive and biocompatible cyclotriphosphazene micelles

Udaya S. Toti, Sun Hee Moon, Hye Young Kim, Yong Joo Jun, Byong Moon Kim, Yong Man Park, Byeongmoon Jeong, Youn Soo Sohn

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


A new class of thermosensitive micellar cyclotriphosphazenes has been synthesized by stepwise nucleophilic substitutions of hexachlorocyclotriphosphazene with a hydrophilic methoxy poly(ethylene glycol) (MPEG) and a hydrophobic oligopeptide selected from tetra- to hexapeptides, and characterized by means of multinuclear (1H, 31P) NMR spectroscopy, elemental analysis, and dynamic light scattering (DLS) method. All the amphiphilic trimers were found to form stable micelles by self-assembly in aqueous solution and to exhibit a lower critical solution temperature in the range of 20-48 °C in water depending on the hydrophilic to hydrophobic balance of the side groups. The micelles formed from the trimers bearing MPEG350 and a tetra- or pentapeptide were found to have a mean diameter of 13-14 nm, while, surprisingly, the trimers bearing longer MPEG550 and hexapeptides have shown remarkable contraction of their micelle size to a mean diameter of 7-8 nm, probably due to the strong intermolecular hydrophobic interactions among the hexapeptide groups of the trimers. The local tolerance tests using rabbits have shown excellent biocompatibility of the trimers. Also a promising in vitro releasing profile was obtained for local delivery of human growth hormone (hGH) as a model protein drug.

Original languageEnglish
Pages (from-to)34-40
Number of pages7
JournalJournal of Controlled Release
Issue number1
StatePublished - 14 May 2007

Bibliographical note

Funding Information:
This work was supported by the SRC program of the Korea Science and Engineering Foundation through the Center for Intelligent Nano-Bio Materials at Ewha Womans University (Grant R11-2005-008-01002-0), by a Korean Research Foundation Grant (KRF-2004-005-C00090), by Seoul R&BD Program, and by Ministry of Commerce, Industry and Energy of Korea.


  • Amphiphile
  • Cyclotriphosphazene
  • Micelle
  • Oligopeptide
  • Thermosensitivity


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