Thermo-responsive Block Copolymers Decorated with Guanosine for the Delivery of Gemcitabine

Abstract

Pancreatic cancer is an aggressive and debilitating human cancer. Due to lack of symptoms and limited diagnostic methods, once diagnosed, the chance for survival is ominous. Gemcitabine has been studied extensively in a variety of tumours and has been found to be effective as a single agent in the treatment of pancreatic cancer. Gemcitabine is a nucleoside analogue of deoxycytidine. Nucleoside antimetabolites have long been the most successful class of anticancer drugs, due to their optimised structures. They are engineered and designed specifically to target DNA synthesis. Nucleosides are known to form complementary hydrogen bonds between base pairs, in this case guanosine. The interaction with guanosine was identified as a potential method of encapsulating gemcitabine. A biocompatible, thermo-responsive polymer was successfully synthesised by using a copolymer with NiPAAm. RAFT, a controlled living radical polymerisation technique pioneered in Australia, was used to produce moderately narrow polydispersed polymers. The polymer properties were subsequently investigated. Solution properties demonstrated self-assembly at near physiological temperature 33°C. Cytotoxicity testing revealed the polymer to be biocompatible and the gemcitabine loaded polymer had improved toxicity than the current administered form. The loading capacity for the micelle was low however, this has set an impetus to improve