메틸셀룰로오즈 기반 약물전달용 온도감응성 주입형 하이드로젤에 관한 연구

Abstract

Recent advances in pharmaceutical biotechnology have produced various kinds of drugs including anticancer agents and recombinant proteins and peptides have been developed for the treatment of diseases such as cancer, diabetes and ischemic heart diseases. Although recent studies in biotechnology have introduced a wide variety of biopharmaceuticals and improved the efficacy and bio-activity of conventional drugs, there are still limitations in the application for clinical studies. The long-term stability in blood stream is a major challenge to be improved in the case of protein and peptide therapeutics, and poor solubility in water and side effects in normal tissues are main limitations of anticancer drugs. Novel drug delivery systems have been studied and developed as the solution to overcome limitations of therapeutic agents. Polymeric micelle, lipid-based carrier, micro-, nano-particles and hydrogel systems for delivery of anticancer drug, therapeutic proteins and peptides are already in the market and envisaged to advance for efficient biopharmaceutical drug delivery. Previously, we reported injectable and thermo-reversible gel using complex coacervates between two oppositely charged biomacromolecules and subsequently co-formulating with a negative thermo-sensitive polysaccharide (methylcellulose) containing a salting-out salt. Although this system showed synergistic effects on complex coacervate formation and sustained release patterns of a model protein drugs, formulation of hydrogel should be simplified and molecular weight of polymer should be reduced for clinical application. In the present study, methylcellulose based thermo-reversible and injectable hydrogel system was developed for the delivery of anticancer drug, docetaxel, fusion protein of PTD-heat shock protein 27, interleukin-1 receptor antagonist, fibroblast growth factor-21 and exenatide. Biophysical characteristics of the hydrogel system were investigated and their therapeutic efficacies were evaluated in vitro as well as in vivo. Although immunogenicity, toxicity and stability of hydrogel system remain to be intensively investigated for clinical applications, the present data will promote future applications of methylcellulose based hydrogel system for delivery of anticancer drug and therapeutic proteins.