Gelation upon the Mixing of Amphiphilic Graft and Triblock Copolymers Containing Enantiomeric Polylactide Segments through Stereocomplex Formation

Biodegradable injectable polymer (IP) systems that form hydrogels in situ when injected into the body have considerable potential as medical materials. In this paper, we report a new two-solution mixed biodegradable IP system that utilizes the stereocomplex (SC) formation of poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA). We synthesized triblock copolymers of PLLA and poly(ethylene glycol), PLLA-b-PEG-b-PLLA (tri-L), and a graft copolymer of dextran (Dex) attached to a PDLA-b-PEG diblock copolymer, Dex-g-(PDLA-b-PEG) (gb-D). We found that a hydrogel can be obtained by mixing gb-D solution and tri-L solution via SC formation. Although it is already known that graft copolymers attached to enantiomeric PLLA and PDLA chains can form an SC hydrogel upon mixing, we revealed that hydrogels can also be formed by a combination of graft and triblock copolymers. In this system (graft vs. triblock), the gelation time was shorter, within 1 min, and the physical strength of the resulting hydrogel (G' > 100 Pa) was higher than when graft copolymers were mixed. Triblock copolymers form micelles (16 nm in diameter) in aqueous solutions and hydrophobic drugs can be easily encapsulated in micelles. In contrast, graft copolymers have the advantage that their molecular weight can be set high, contributing to improved mechanical strength of the obtained hydrogel. Various biologically active polymers can be used as the main chains of graft copolymers, and chemical modification using the remaining functional side chain groups is also easy. Therefore, the developed mixing system with a graft vs. triblock combination can be applied to medical materials as a highly convenient, physically cross-linked IP system.