In situ gelling implants based on temperature-responsive amphiphilic triblock copolymers

In this thesis, emphasis is given to the study of temperature-responsive amphiphilic triblock copolymers and their use for in situ drug delivery systems. Two polymers have been studied with approximately the same composition of the two hydrophobic caprolactone copolymerised with lactic acid (PCLA) end groups. The middle hydrophilic poly(ethylene glycol) (PEG) spacer is different between the polymers; respectively with a molecular weight of 1000 and 1500 g/mol. PCLA-PEG-PCLA is showed to form a gel that is temperature dependent. The polymeric systems were characterised in terms of their rheological properties through laboratory measurements, i.e. gel point, dynamic viscosity, gel properties and thermodynamic features in form of cloud point. It was proven that both the concentration and length of the hydrophilic PEG spacer affects the rheology and structure of the system. A sol-gel-sol (phase separation) transition was observed for both polymer systems via the tube inverting method. It was only possible to determine a critical gel point for the PCLA-PEG(1000)-PCLA polymer. The properties of the polymer with the short PEG spacer, observed from small angle neutron scattering measurements, could be explained by formation of worm-like cylindrical micelles. The polymer with the longer PEG spacer forms flower-like spherical core-shell micelles. It was shown through rheology tests that these cylinders were less stable upon heating and therefore more temperature-responsive