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James R. Baker Jr. University of Michigan Professor, Internal Medicine and Bioengineering Chief, Division of Allergy Director, Center for Biologic Nanotechnology Co-Director, Center for Biomedical Engineering Biotechnology, Nanotechnology and Immunology Drug Delivery • Research in the area of autoimmune endocrine disease. He has helped define the basis of the autoimmune response to thyroid auto antigens. Gene Delivery • Work concerning gene transfer; developing a new vector system for gene transfer using synthetic polymers (dendrimers). Anti-microbial research • Work on preventing pathogens from entering the human body. This research project seeks to develop a composite material that will serve as a pathogen avoidance barrier and post-exposure therapeutic agent to be applied in a topical manner to the skin and mucous membranes. Drug Delivery by dendrimers Project called “smart Bombs”: Target cancerous cells and leave the normal intact. • Recognition and diagnosis of cancer • Drug delivery • Location of c cells • Kill by releasing agents Drug Delivery by dendrimers Dendrimers • Known for several applications • Able to enter cells • Little toxicity Focus: • High energy lasers or sound wave energy to trigger the release of the drug out of the dendrimer. Antimicrobial Nanoemulsion • Use of soybean oil emulsified with surfactants. Drops ~400 – 600 nm. • The droplet do not coalesce with themselves . High surface tension make them coalesce with other lipid droplets, killing bacteria. • Safe for external use. Not safe for red cells, or sperm. • The droplets fuse with cell membrane of microorganisms resulting in cell lysis. • Very effective in killing: – Bacteria, – Bacterial spores, – Enveloped viruses, and – Fungal spores. • They are effective at preventing illness in individuals, when used both before and after exposure to the infective agent. • They could be used: – Topically, – As an inhalant. Antimicrobial Nanoemulsion • Left: treated with nanoemulsion, • Right: untreated. • The growth of bacteria colonies has been eliminated by treatment with nanoemulsion. Gene Transfer • G-5 dendrimers of Poly(amidoamine) • The dendrimer is acetyladed to increase solubility. • Fluorescein is incorporated onto the dendrimer for imaging in vivo. • Folic acid is then conjugated as targeting agent. • The final step is to conjugate the therapeutic drug. Gene Transfer • Into cardiovascular tissues for treatment. • Use of dendrimer/DNA complexes – Uniform size, high density, soluble, stable. • Direct injection or intracoronary delivery. Enhanced expression of beta-galactosidase in electroporated nonvascularized grafts. A. Graft treated as in group 12, Figure 1. B. Graft treated as in group 4, Figure 1. (Original magnification 40).