Synthesis and characterization of sulfated poly-amido-saccharides and block poly-amido-saccharides for biomedical applications

Polyamides are versatile polymers and includes naturally occurring macromolecules such as proteins as well as purely synthetic materials such as Nylon-3 and Nylon-6 polymers. While there are different ways to prepare polyamides, polyamide synthesis using anionic ring opening polymerization of lactams is the most widely used technique, due to the ease in preparation, excellent control in molecular weight and availability of wide variety of monomers. Our group reported the preparation of carbohydrate-based polyamides called poly-amido-saccharides (PASs) using anionic ring opening polymerization of sugar b-lactam monomers. The PASs reported so far includes glucose, galactose, altrose and maltose PASs, and functional PASs with n-octyl, carboxylate and amine functionalities. Sulfated or block poly-amido-saccharides on the other hand are unknown. In this thesis, I describe the synthesis of sulfated and block poly-amidosaccharides as well as evaluation of their biomedical applications. Naturally occurring sulfated polysaccharides play important roles in anticoagulation, lubrication of cartilage, and in developmental processes. New glucose-based non-regioselectively and regioselectively sulfated poly-amido-saccharides are prepared by the polymerization of protected glucose b-lactams, followed by post-polymerization modification reactions. All polymers are water soluble, non-cytotoxic, and adopt helical conformations. I evaluated the anticoagulant activity of the sulfated polymers using in vitro, ex vivo, and in vivo methods as well as determined the mechanism of anticoagulation by amidolytic activity inhibition assays. Additionally, I synthesized new block copolymers as block copolymers are used for various applications including latex paints and pressure sensitive adhesives. Specifically, carbohydrate-based amphiphilic polymers are of interest for drug delivery applications, due to favorable properties such as cytocompatibility, low immunogenicity, and longer circulation time. We prepared PAS-based amphiphilic block polymers with varied polymer length, hydrophobic to hydrophilic ratio, and stereochemistry of hydrophilic component. I characterized these amphiphilic polymers by NMR, IR, GPC, DSC, TGA and CD, and they self-assemble in water to form nanostructures as determined by DLS, SEM, and cryo-TEM, and are non-cytotoxic.2024-11-16T00:00:00