Peptide‐Functionalized Thermo‐Sensitive Hydrogels for Sustained Drug Delivery

Abstract

Abstract In this study, a KRGDKK (Lys‐Arg‐Gly‐Asp‐Lys‐Lys) peptide with a RGD sequence is utilized as a functional group to synthesize a novel thermo‐sensitive hydrogel. The KRGDKK peptide prepared by a solid phase synthesis approach is coupled to the ends of a poly[( ε ‐caprolactone)‐ co ‐lactide]‐poly(ethylene glycol)‐poly[( ε ‐caprolactone)‐ co ‐lactide] (PCLA‐PEG‐PCLA) triblock copolymer to obtain peptide‐PCLA‐PEG‐PCLA‐peptide. The self‐assembly behavior of both PCLA‐PEG‐PCLA and peptide‐PCLA‐PEG‐PCLA‐peptide copolymers in aqueous solution is investigated, and hydrogels prepared from PCLA‐PEG‐PCLA and peptide‐PCLA‐PEG‐PCLA‐peptide are also prepared. An in vitro cell viability study demonstrated that the peptide‐PCLA‐PEG‐PCLA‐peptide hydrogels do not exhibit an apparent cytotoxicity, which suggests that the hydrogels have promising potential as injectable drug‐delivery systems. Furthermore, compared with the PCLA‐PEG‐PCLA hydrogels, the peptide‐PCLA‐PEG‐PCLA‐peptide hydrogels display improved mechanical properties because of hydrogen bonding between the amino groups of KRGDKK. An in vitro drug release study showed that the peptide‐PCLA‐PEG‐PCLA‐peptide hydrogels exhibit outstanding controlled release properties and the release of the drug could be sustained for more than a month without initial burst. magnified image