163ac Temperature-Sensitive Copolymers of N-Isopropyl-Acrylamide and N,N-Dimethylacrylamide: Application in Hyperthermia-Directed Gene Delivery

Ramesh Rajasekaran, Ye-Zi You, and David Oupicky. Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201

Temperature-responsive copolymers based on N-isopropylacrylamide (NIPA) undergo strong conformational changes in shape, size, and solubility that are induced by small changes in the temperature. Such copolymers are useful in various biomedical applications such as drug delivery, tissue engineering, or biomimetic actuators. Clinical application of hyperthermia involves raising the temperature of a tissue in order to achieve a therapeutic effect (e.g. tumor to treat cancer). The temperature increase of tissues to 40–43°C can be achieved with high precision using various methods including focused ultrasound and microwaves. To design delivery vectors suitable for hyperthermia-directed gene delivery, we have synthesized copolymers of NIPA with N,N-dimethylacrylamide (DMA). The copolymerization of NIPA with DMA allowed adjusting the phase transition temperature of the copolymers to temperature compatible with clinical hyperthermia protocols. The copolymers were characterized by various methods including light scattering and differential scanning calorimetry. Application of the synthesized copolymers in the design of gene delivery vectors will be presented and the potential of the vectors in hyperthermia targeting discussed.