Design and Development of Nanogels for Small Molecule and siRNA Delivery

Encapsulating drug molecules, and selectively delivering those drugs to a disease site, is a complex multi-step challenge that requires the consideration of several interrelated parameters. We have developed stimuli sensitive nanogels that offer the size, stability, release kinetics, and drug loading capabilities necessary for efficient delivery. Our nanogel design is versatile and can be adapted to drug, gene, and protein delivery with little manipulation to its structure. In this thesis, we improve on the nanogel design by addressing a critical step in material based drug delivery, which is endosomal escape. We show how both functional groups on the delivery system as well as its architecture are important factors in deciding its escape from the endosome. Further, we expand the scope of nanogels for siRNA delivery using systematic design approaches. We demonstrate by employing concepts of supramolecular chemistry, adopted from our nanogel designs, we can systematically design a delivery vehicle of lower toxicity while achieving better complexation to siRNA, in comparison to simple polycationic homopolymers. Finally, we further improve upon our nanogel designs so as to allow for better biodegradability and biocompatibility by synthesizing nanogels using biocompatible GRAS building blocks