In situ photo‐crosslinked hydrogels prepared from acrylated 4‐arm‐poly(ethylene glycol)‐poly(ε‐caprolactone) block copolymers for local cancer therapy

Abstract

AbstractAmphiphilic block copolymers were synthesized by ring‐opening polymerization of ε‐caprolactone (ε‐CL) using 4‐arm poly(ethylene glycol) (4aPEG) as macroinitiator. 4aPEG and 4aPEG‐PCL copolymers were end functionalized by introducing acrylic groups, and characterized using NMR, GPC, FT‐IR and DSC analyses. Photo‐crosslinked hydrogels were prepared by irradiation of acrylated polymer solutions under visible light (405 nm), using lithium phenyl‐2,4,6‐trimethylbenzoy‐lphosphinate (LAP) as a photoinitiator. In situ gelation was achieved by subcutaneous injection of LAP containing copolymer solution into the abdomen of mice, followed by exposure to visible light. The hydrogels exhibit highly porous structure, high swelling up to 3300%, and excellent biocompatibility. The swelling ratio decreases with increase of poly(ɛ‐caprolactone) (PCL) block length and polymer concentration of hydrogels. Doxorubicin hydrochloride (DOX·HCl) was loaded in hydrogels by soaking dried gel in a DOX solution. The drug loading efficiency is dependent on the swelling performance, reaching a maximum of 94.3%. In vitro drug release studies showed a burst release for the first 6 h, followed by a slower release up to 82% at 28 days. The release rate decreased with increase of hydrophobic block length or polymer concentration of hydrogels. Higher anti‐cancer activity on A549 lung cancer cells was obtained for hydrogels with higher drug concentration, and shorter PCL block length. Therefore, 4aPEG‐PCL hydrogels with outstanding biocompatibility, in situ gelation and prolonged drug release could be very promising for long‐term local cancer therapy.