Novel pH and Temperature Sensitive Injectable Hydrogels and MicellesDoo Sung LeeDept. of Polymer Sci. and Eng., Sungkyunkwan Univ., Korea
The synthetic polymers have attracted significant attention in the drug delivery systems. The synthetic polymers are able to delivery the drug to target-site and minimize the side-effect of drug, used as a component of a drug product for the purpose of eliciting or modifying drug action. In this study, hydrophilic and hydrophobic block length of block copolymer was controlled in order to increase in vivo stability of block copolymer micelle and hydrogel. Also, the pH sensitive moiety helps for the micellization and gelation in block copolymer.We synthesized the pH sensitive biodegradable block copolymer successfully such as MPEG-poly(β-amino esters). The critical micelle concentration (CMC) of the block copolymer was studied by the steady state fluorescence method in various buffer solutions. According the poly(β-amino ester) was fully ionized below pH 7.0, the block copolymer didn’t form the micelle. However, as the pH of solutions was increased above 7.0, the poly(β-amino ester) began to be deionized. Therefore, the block copolymer was formed the micelle with increasing the pH. The micelle of this copolymer was shown the critical pH-sensitivity in the narrow pH range.The sol (flow) ? gel (no flow) phase transition temperature of pH & thermo-sensitive block copolymers of type I and type II in buffer solution was observed for the polymer containing pH sensitive group. They show a sensitive, reversible sol-gel transition with a small pH range (less than pH 0.8) and a temperature change in the region of the body temperature. These pH and temperature sensitive hydrogels were prepared by the very precise molecular weight control of block copolymer and the prudential tuning of hydrophilic-hydrophobic balance. These hydrogels remain on the gel state in buffer solution (pH 7.4, 37 ℃) for a long time (more than 2 weeks), and the pH of the gel does not changes by the degradation of the aliphatic polyester block. It is expected that these pH and temperature sensitive hydrogels will be able to be used in injectable systems for hydrophobic drugs, proteins and cells etc. Moreover, because they do not change into gel form only with increasing temperature, they can also be employed as injectable carriers, using a long guide catheter into the body.References
1. G. Chen and A. S. Hoffman. Nature 373, 49-52 (1995)
2. Jeong BM, Bae YH, Lee DS, Kim SW. Nature 388, 860-862 (1997)