Temperature/pH Responsive Hydrogels Based on Poly Block Copolymers for Controlled Delivery of Macromolecules

Purpose To assess the potential of triblock copolymers based on poly(ethylene glycol) (PEG) and functionalized poly([epsilon]-caprolactone) as temperature/pH responsive gels for controlled delivery of macromolecules. Methods Poly([alpha]-carboxylate-co-[alpha]-benzylcarboxylate-[epsilon]-caprolactone)-PEG-poly([alpha]-carboxylate-co-[alpha]-benzylcarboxylate-[epsilon]-caprolactone) (PCBCL-PEG-PCBCL) was synthesized through ring opening polymerization of [alpha]-benzyl carboxylate-[epsilon]-caprolactone by PEG, followed by 30% debenzylation of the lateral blocks. The effect of Tris buffer and pH on the sol-gel transition temperature of PCBCL-PEG-PCBCL was assessed. The temperature/pH responsive release of tetramethylrhodamine-dextran (TMR-D) (10 and 40 kDa) from PCBCL-PEG-PCBCL was investigated. Results Replacement of water with Tris buffer reduced PCBCL-PEG-PCBCL sol-gel transition temperature. Thermo-reversible hydrogels were only formed at pHs [greater than or equal to] 5.0, but PCBCL-PEG-PCBCL transition temperature was not affected by pH above pH 5.0. In contrast to Pluronic F127 that released 100% of TMR-D within 2 h, PCBCL-PEG-PCBCL hydrogel controlled TMR-D release efficiently at pH = 7.4 and 37°C (~27 and 11% TMRD 10 and 40 kDa release within 150 h, respectively). At 50°C or pH = 9.0, TMR-D release was increased slightly, while at room temperature or pH = 5.0, no control over TMR-D release was observed by PCBCL-PEG-PCBCL hydrogel. Conclusion PCBCL-PEG-PCBCL hydrogel provides depot release of macromolecules at physiological conditions. This release can be triggered through changes in the temperature or pH.