약물전달용 온도 감응성 젤에 대한 연구

Abstract

ABSTRACT

Studies on Thermo-reversible gel for drug delivery

Jang Kyoung, Kim Dept. of Bioengineering The Graduate School Hangyang University

We characterized thermo-reversible hydrogels for hydrophilic and hydrophobic drug delivery. For hydrophilic drug delivery, natural polymer low molecular weight methylcellulose(LMw MC), salting-out salt, ammonium sulfate(AS) were used and proteins were coacervated with protamine for sustained release of drugs. The gelling temperature and viscosity result demonstrate that LMw MC / AS hydrogels are solution state in low temperature but it can be changed to gel state by increasing of temperature. So Our hydrogels for drug delivery can be easily injected by syringe to the animal and human, injected hydrogels can be changed to gel state and loaded drugs can be released from hydrogels. in vitro release profile was tested using fitc-BSA, PTD-Hsp 27 and interleukin-1 receptor antagonist(IL-1Ra). Although PTD-Hsp 27 was not need coacervation, proteins were coacervated with protamine and released from hydrogels slowly. Moreover result of hematoxylin and eosin staining showed that hydrogels are biocompatible because there were no inflammatory reaction in hydrogels injected area. For hydrophobic drug delivery, hydrogels were made with LMw MC, pluronic F127 polymer and AS. This hydrogels showed sol-gel transition property by temperature, this property was reversible, and was not changed after Cy5.5 conjugation. The docetaxel(DTX), hydrophobic anti-cancer drug, was easily loaded to optimized hydrogels, and in vitro release profiles of DTX showed that sustained release manner with minimal initial burst over 30 days. We also evaluated anti-cancer efficacy of DTX loaded hydrogels using measurement of tumor volume and live animal imaging technology. The DTX loaded hydrogels showed higher anti-cancer efficacy with reduced tumor volume, increased survival rate and reduced luciferase intensity in B16-F10-luc melanoma cancer cell bearing mice. The biodegradation and bioelimination result using Cy5.5 conjugated hydrogels showed that our hydrogels were degraded in vivo condition and eliminated by liver and kidney. So our hydrogels can deliver hydrophilic protein drug and hydrophobic anti-cancer drug with sustained release profile and showed promising application to protein drug delivery and anti-cancer therapy without cytotoxicity.