Controlled thermal gelation of poly(ε-caprolactone)/poly(ethylene glycol) block copolymers by modifying cyclic ether pendant groups on poly(ε-caprolactone)

Abstract

The control of the thermal gelation behavior of amphiphilic copolymers based on PEGylated hydrophobic polymers is important for applications in drug administration and controlled release. This paper studied a new method to control the thermal gelation behavior of the amphiphilic copolymers by structure modification of hydrophobic segments. A kind of triblock copolymer of PEG and modified poly(ε-caprolactone) (PCL) with cyclic ether pendant groups, i.e. poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) triblock copolymers (PECT) were synthesized through the ring-opening copolymerization of ε-caprolactone and 1,4,8-trioxa[4.6]spiro-9-undecanone (TOSUO) in the presence of poly(ethylene glycol). The structure and thermal gelation behavior of PECT were characterized by ¹H NMR, FT-IR, GPC, XRD, DSC and DLS, etc. The study results indicated that the introduction of cyclic ether pendant groups on the PCL backbone not only reduced the crystallinity of PCL but also increased the hydrophilicity of the hydrophobic phase, which provides perfect dispersity of PECT in water and allows a more excellently controlled thermal gelation behavior than the PCL-PEG-PCL block copolymer. PECT powder can directly disperse in water to form a stable nanoparticle aqueous dispersion even with a high content of hydrophobic block (the weight ratio of PCL to PEG is nearly 3). Further, the PECT nanoparticle aqueous dispersion at higher concentration performed sol–gel–sol transition behavior with the temperature increasing from ambient or lower temperature, and the transition temperature and gelation behavior could be adjusted by the content of the cyclic ether pendant groups on the PCL segments. Significantly, avoiding the pre-quenching treatment that is needed for PCL-PEG-PCL gelation, the PECT nanoparticle aqueous dispersions, which are injectable fluids at ambient temperature and form a gel at 37 °C quickly, provide an injectable in situ gel system for clinical applications with the advantages of convenient dosage, administration, storage, and prescription. Therefore, the PECT thermal hydrogel system is expected to have potential applications in drug delivery and tissue engineering.