Poly(ε-caprolactone) with pH and UCST responsiveness as a 5-fluorouracil carrier

Stimuli-responsive polymers with excellent biocompatibility and biodegradability are highly demanded as carriers for controlled drug delivery. Herein, a functional poly(ε-caprolactone) (PCL) of poly(6-acetoxyl-ε-caprolactone)-graft-(6-methyluracil) (PCCL-g-MU) was synthesized via post modification of poly(6-acetoxyl-ε-caprolactone) (PCCL) with 6-(chloromethyl) uracil (MU). The incorporation of carboxyl and uracil groups endowed the PCL backbone with both pH and upper critical solution temperature (UCST) responsiveness. Benefiting from the structural similarity between MU and the anticancer drug 5-fluorouracil (5-FU), the self-assembled PCCL-g-MU nanoparticles resulted in a high 5-FU loading efficiency of 42%. Temperature-dependent release behavior of 5-FU loaded PCCL-g-MU nanoparticles was found to have originated from UCST transition. MTT assay against the L929 cell line revealed low cytotoxicity of PCCL-g-MU nanoparticles. The hydrolysis of the PCL backbone in either PBS or enzymatic solution indicated excellent biodegradability of PCCL-g-MU. It was demonstrated for the first time that biodegradable poly(ε-caprolactone) with UCST behavior was developed, which is significant for enriching the thermo-responsive polymer library as well as biomedical applications.