Polymer Nanostructure and Property Laboratory

Injectable Hydrogels
Stimuli-sensitive hydrogels have attracted considerable attention as intelligent materials in the fields of biochemistry and biomedicine due to their ability to detect environmental changes and undergo structural changes by themselves such as solubility and swelling ratio. Among the developed stimuli-sensitive materials, polymers showing a sol-to-gel transition with changing temperature have been proposed for use as injectable drug delivery systems. These hydrogels, however, have several unresolved drawbacks that limit their potential as injectable drug delivery systems. When temperature-sensitive hydrogels are injected into the body via syringe, the warmth of the body tends to cause gels to form within the needle, to inject into the body. Also, after injection, the hydrogels tend to undergo the rapid degradation of the block copolymer, resulting in the formation of an acidic monomer such as lactic or glycolic acid. It decreases the pH of the hydrogel. Consequently, the low pH environment associated with the hydrogel is known to be deleterious to some proteins and nucleic acids, such that the pH change that occurs within these biodegradable hydrogels is an important consideration. We designed the novel block copolymers composed of the temperature-sensitive block and pH sensitive block to fabricate thermo and pH sensitive injectable hydrogel. As shown in Figure 1, their sol-gel transition behavior was controllable depending on the introduced chargeable block. In our laboratory, sulfonamide and poly(β-amino ester) were considered as pH-sensitive block using their anionic and cationic property, respectively. We are trying to use as these injectable hydrogels for protein delivery and tissue engineering.
pH-Sensitive Micelles
There is increasing interest in pH-sensitive polymers because of their many potential applications in biotechnology, including drug delivery systems and sensors. In particular, micelle-forming pH-sensitive copolymers are very useful tools for targeting the delivery of hydrophobic drugs both to acidic tumor tissues (pH 6.0 to 7.2), compared to normal tissue (pH 7.4), and to the cytoplasm after the release of endosome (pH 5.5). pH-dependent solubility is generally employed in pH-sensitive polymers. Ionization makes polymers with acidic character, such as poly(sulfonamide), soluble above the pKa value but insoluble below it. In contrast, polymers with alkaline character, such as poly(β-amino ester) (PAE) and poly(L-histidine), are insoluble at high pH values but soluble at low ones, due to their ionization properties. In our laboratory, poly(ethylene glycol) was combined with PAE to obtain an amphiphilic block copolymer. The methoxypoly(ethylene glycol)-poly(β-amino ester) block copolymer can form self-assembled micelles depending on the pH value, that is, micelles are formed at a pH of 7.4, but the copolymer is fully solubilized at lower pH values. Doxorubicin-loaded micelles were quite effective in cancer therapy. Using this pH-sensitive micelle, we are trying to evaluate the efficacy for carriers of therapeutic or diagnostic agent.