Controlled dual release of basic fibroblast growth factor and indomethacin from heparin-conjugated polymeric micelle

Jung Seok Lee, Jin Woo Bae, Yoon Ki Joung, Seung Jin Lee, Dong Keun Han, Ki Dong Park

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


This work describes the development of heparinized polymeric micelle as a novel injectable carrier for the dual drug delivery that can simultaneously release basic fibroblast growth factor (bFGF) and indomethacin (IMC), which can promote the regeneration of damaged tissue and prevent the inflammatory response after implantation. Tetronic®-PCL-heparin for the preparation of heparinized polymeric micelle was synthesized by introducing PCL as a biodegradable linkage on Tetronic, following the conjugation of heparin. The mean diameter of the formed TCH micelle was around 114 nm and increases in the micelle size after single and dual drug loading were observed. Loading efficiencies of IMC and bFGF were 30.9% and 70.5%, respectively. In vitro dual drug release profiles from TCH micelles were investigated. IMC was more slowly released from dual drug-loaded micelle over 3 weeks as compared with single drug-loaded one. bFGF was released over 2 months in a controlled manner. Therefore, the release profile results support that TCH micelle could not only incorporate a hydrophobic drug into the core but also bind with bFGF to heparin that exists on its outer shell. The TCH micelle will have enhanced therapeutic effects on the target site which may be required the multi-function of drugs to use.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalInternational Journal of Pharmaceutics
Issue number1-2
StatePublished - 4 Jan 2008

Bibliographical note

Funding Information:
This work was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare (02-PJ3-PG6-EV11-0002), and Nano-Biotechnology Project (Regenomics), Ministry of Science & Technology (B020214), Republic of Korea.


  • Dual drug release
  • Growth factors
  • Heparin
  • Polymeric micelle
  • Tissue engineering


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