Responsive polypeptide containing block copolymers and polymer particles

The synthesis and characterisation of novel stimuli-responsive polymers designed for biomedical applications is described. The first system is temperature-sensitive and is foreseen as useful for the study of the influence of particle shape on cellular uptake while the second one for the redox-sensitive delivery of drugs.

Chapter 1 contains a background on the field of synthetic polymers for biomedical applications and on the polymerisation techniques applied by researchers and particularly in this work, namely RAFT and NCA polymerisations. In Chapter 2 the combination of these two techniques is described to yield poly[(BLG)_m-b-(NIPAM)₇₉-b-(PEGA)_p] block copolymers. In Chapter 3 the formulation and characterisation of the particles formulated from these block copolymers are discussed. These particles are temperature responsive due to the presence of the middle NIPAM block and additionally they can adopt either anisotropic or spherical shape depending on the organic solvent used in their formulation procedure. The ability to switch between two shapes makes them suitable candidates for the study of the influence of particles shape on cellular uptake. Modifications to these copolymers applied in the attempt to make them fluorescent are presented in Chapter 4.

Chapter 5 describes the synthesis and preliminary release studies of a redox-sensitive block copolypept(o)ide of formula poly[(Glu)_m-b-(Sar)_n]. The polymer side chains were functionalised to include a disulfide bond with the drug 6-mercaptopurine. The prodrug obtained was able to release its cargo in a reductive environment faster than in PBS.

Finally, Chapter 6 offers an overview of the steps planned for further development of these systems.