| 학회 | 한국고분자학회 |
| 학술대회 | 2005년 가을 (10/13 ~ 10/14, 제주 ICC) |
| 권호 | 30권 2호 |
| 발표분야 | 의료용 고분자 부문위원회 |
| 제목 | Heparin Functionalized Tetronic-PCL Micelles that modulate Controlled Release for Drug Delivery of Growth Factors |
| 초록 | Recently, an amphiphilic polymeric micelle (PMs) with the intrinsic interest in self-assembling systems is familiar with most of the investigators researching into drug delivery system. The core-shell structure of PMs provides the potential for use as vehicles for drug delivery since the hydrophobic core may serve as a container for drugs, which is segregated from the outer environment by a palisade-like hydrophilic segment and a driving force of the spontaneous micelle formation. And the hydrophilic shell pays an important role in absorption of drug carrier since it derives a well-dispersion property in aqueous environment. These PM systems have been mainly studied as a carrier for hydrophobic drugs due to their structural characteristics under aqueous condition, and consequently have limitations in the control of drug loading and release kinetics for hydrophilic drugs such as proteins and peptides. Heparin as a representative antithrombotic drug has been shown to interact with a number of biologically important proteinssuch as growth factors and cytokines, thereby playing an essential role in the regulation of various physiological processes.Based on these specific interactions between heparin and proteins, the conjugation of heparin to amphiphilic polymer can be advantageous for the design of PMs for protein delivery. In this study, we developed new PM system for protein delivery by conjugation of heparin to block copolymer that consists of Tetronic and PCL (poly(ε-caprolactone)). Tetronic as poloxamer derivatives is a surfactant which is thermo-sensitive and nonionic tetra-functional block copolymer with four PEO-PPO blocks. PCL as a well-known biodegradable polymer in biomedical field has good biocompatibility and the biodegradability PCL blocks can help the sustained release of the heparin and the heparin binding proteins. Accordingly, Tetronic-PCL-heparinmicelle as a protein carrier is expected to be useful for inducing the cell growth and cell proliferation in tissue engineering application. Amphiphilic multiblock Tetronic-PCL copolymer was synthesized by a ring-opening polymerization of ε-caprolactone with Tetronic using stannous octoate as a catalyst, and Tetronic-PCL-heparin conjugate was prepared by coupling heparin with Tetronic-PCL copolymer using EDC/NHS as coupling agents. The physicochemical properties of these polymers were examined by 1H-NMR, FT-IR and GPC. The contents of bound heparin are measured to be 0.44㎍/㎍ and the heparin activity measured by APTT assay is shown to be 43.6% as compared to free heparin. To estimate their feasibility as a polymeric vehicle for protein delivery, the critical micelle concentration (CMC) of micelles prepared from self-assembly under aqueous condition was determined by a fluorescence probe technique using pyrene. The diameters of Tetronic-PCL micelle in number averaged scale was observed around 25nm and its size after heparin coupling was increased to 224nm due to heparin chain located on hydrophilic shell of the micelle. Therefore, we suggest that Tetronic-PCL-heparin micelle can be useful as a good candidate forthe sustained delivery of various proteins with heparin-binding domain in pharmaceutical fields. |
| 저자 | 이중석, 고동현, 박기동 |
| 소속 | 아주대 |
| 키워드 | Tetronic; Heparin; Micelle; Growth Factor; Drug Delivery System |
