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

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. Drug Delivery by dendrimers

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.

Left: treated with nanoemulsion, Right: untreated. The growth of bacteria colonies has been eliminated by treatment with nanoemulsion. Antimicrobial 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.

Into cardiovascular tissues for treatment. Use of dendrimer/DNA complexes –Uniform size, high density, soluble, stable. Direct injection or intracoronary delivery. Gene Transfer

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).