The intracellular delivery of nucleic acids offers promise for revolutionizing biomedical research and novel drug development.  Likewise, small molecule drug and vaccine development could significantly benefit from new materials that aid targeted delivery.  However, the polymeric delivery vehicle plays a central role in dictating the efficacy, safety, mechanisms, and kinetics of drug transport.  We have developed several novel carbohydrate-containing polymers that have shown outstanding affinity to encapsulate polynucleotides, drugs, and peptides into nanocomplexes and facilitate highly efficient intracellular delivery without toxicity.  A series of nine poly(2-deoxy-2-methacrylamido glucopyranose)-b-poly(methacrylate amine) diblock copolycations have been  synthesized as new colloidally-stable polynucleotide vehicles.  The cationic block was varied in length and in the degree of methyl group substitution (secondary, tertiary, quaternary) on the pendant amine in an effort to optimize the structure and activity for plasmid DNA delivery. Upon a thorough kinetic study of polymerization for each polymer, the glycopolymers were prepared with well-controlled Mn and �. The binding and colloidal stability of the polymer-pDNA nanocomplexes at different N/P ratios and in biological media has been investigated using gel electrophoresis and light scattering techniques. The toxicity and transfection efficiency of the polyplexes has been evaluated with Hep G2 (human liver hepatocellular carcinoma) cells; several polymers displayed excellent delivery and toxicity profiles justifying their further development for in vivo nucleic acid delivery.

Optimization of diblock glycopolycations for drug and nucleic acid delivery

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.