Development and Evaluation of Cyclodextrin Based Materials for Applications in Gene Therapeutics

Therapeutic applications of gene therapeutics in human has attracted numerous opportunities that exist in treating cancer, neurological disorders, and cardiovascular diseases. In this arena, nanoparticle-mediated pDNA and siRNA (small interfering RNA) delivery is a potential method of choice, yet the unmet challenges such as high efficiency, lower toxicity and clinical suitability limits its applications. Moreover, processes required for transport of these materials across the extracellular and intracellular barriers are poorly understood. Efficient delivery of gene-containing nanoparticles would benefit from an improved understanding of how parameters associated with these barriers relate to the physicochemical properties of the nanoparticle vectors. Herein, a family of cyclodextrin based materials has been developed based on non-covalent interactions and self-assembly for the purpose of nucleic acid delivery. The results suggest that the hyaluronic acid based pendant polymer:cationic CD complexes and cationic polyrotaxanes designed here for pDNA and siRNA delivery are viable candidates for in vivo translation due to their low toxicity, attractive physical characteristics and efficacy.