Degradable/cytocompatible and pH responsive amphiphilic conetwork gels based on agarose-graft copolymers and polycaprolactone

Amphiphilic conetwork (APCN) gels have emerged as an important class of biomaterials due to their diverse applications. APCN gels based on biocompatible/biodegradable polymers are useful for controlled release and tissue engineering applications. Herein, we report a facile synthesis of APCN gel films by click type sequential nucleophilic substitution reaction between pendent tertiary amine groups of agarose-g-poly(methyl methacrylate)-b(co)-poly(2-dimethylamino)ethyl methacrylate [Agr-g-PMMA-b(co)-PDMA] copolymers and activated benzyl chloride groups of polychloromethyl styrene or benzyl methyl chloride terminated polycaprolactone. A linear triblock copolymer (PDMA-b-PMMA-b-PDMA) containing a central PMMA block and end PDMA blocks was also employed for the synthesis of APCN gels for comparison purposes. These APCN gels exhibit co-continuous nanophase morphology, pH responsive water swelling and pH triggered release of hydrophobic and hydrophilic drugs. These gels are biodegradable/cytocompatible as confirmed by MTT assay and hemolysis experiment. The degraded species undergo micellization in aqueous environment and display a low critical micelle concentration. Milled APCN gel particles are injectable through a hypodermic syringe. This synthesis approach is extremely useful for the preparation of a library of APCN gels of diverse architectures and compositions for biomedical applications.