초록 |
In situ hydrogel formation without incorporating organic solvents have recently drawn great attention in the biomaterial community due to their high impact on delivery applications of water-insouble anticancer drugs, peptide/protein pharmaceuticals, genetic materials, and cells. Upon injection of an aqueous polymer solution which contains bioactive components into a body compartment, stable physical hydrogels can be formed by temperature-induced sol-to-gel transition. Although the thermal gelation has long been known with natural macromolecules via varying gelation mechanism, recent synthetic biodegradable polymers have triggered extensive researches for the molecular design of amphiphilic polymer architectures for specific properties and biomedical/pharmaceutical purposes. Most of all, the deep-site application of hydrogel/bioactive components is highly desired. This can be coupled with the advanced technologies of cannulation and catheterization and microsurgery such as laparoscopic operation, which become relevant to aforementioned delivery systems. However, the sol-to-gel transition by temperature is a suboptimal condition for applying hydrogels for deep anatomical sites in the body due to thermal equilibration during the delivery process of the solution through a narrow conduit, resulting in premature gelation inside the conduits or tubings. Here we report a tailored polymeric material of which aqueous solutions undergo sol-to-gel transition by both physiological pH and temperature. The pH and temperature sensitive block copolymer hydrogel undergoes a sensitive, reversible sol-gel transition when the pH is changed within a small range (pH 7.4 - 8.0), as well as when the temperature is changed. As the block copolymer solution (pH 8.0, room temperature) was injected in buffer solution (pH 7.4, 37 oC), it was not solubilized by dilution, but formed the gel. Also, the pH of the OSM-PCLA-PEG-PCLA-OSM block copolymer hydrogel did not change over a relatively long period of time. This hydrogel could be a platform material for the development of a pH sensitive injectable carrier for hydrophobic drugs, protein and cell delivery. |