Poly(amidoamine) (PAMAM) dendrimer interactions with biological membranes. Left panel: Atomic force microscopy (AFM) observation of dimyristoylphoshatidylcholine (DMPC) supported lipid bilayers (a), (c), and (e) before and after incubation with (b) G7‐NH2, (d) G5‐NH2, and (f) G5‐Ac PAMAM dendrimers, respectively. Middle panel: Space‐filling models of chemical structures of (a) G7‐NH2, (b) G5‐NH2, and (c) G5‐Ac PAMAM dendrimers. Right panel: Lactate dehydrogenase (LDH) leakage as a result of cell exposure to PAMAM dendrimers. (a) Size effect of G7‐NH2 and G5‐NH2 on the LDH leakage out of KB and Rat2 cells after incubation at 37°C for 3 h and (b) surface group dependency on the LDH leakage at different temperatures. Note that larger dendrimers (G7‐NH2) induce formation of new nanoscale holes in the bilayers as seen in the AFM images and cause more amount of LDH leakage out of live cells than G5‐NH2. G5‐NH2 dendrimers do not cause new hole formation in the lipid bilayers but instead expand preexisting defects. In contrast, G5‐Ac dendrimers do not cause hole formation, expansion of preexisting defects, or LDH leakage out of live cells. (Reprinted with permission from Ref 33. Copyright 2007 American Chemical Society) .
(a) A snapshot at the beginning (0 ns) of the simulation of system G5‐1 (100% acetylated). Snapshots at the end (0.5 µs) of simulations of systems (b) G5‐1, (c) G5‐2 (50% acetylated), (d) G5‐3 (un‐acetylated), (e) G5‐4 (un‐acetylated, 500 mM NaCl), (f) G5‐5 (un‐acetylated, low temperature), (g) G3‐1 (100% acetylated), and (h) G3‐2 (un‐acetylated). Black dots represent dendrimers, and blue dots represent head groups of the dipalmitoylphosphatidyl choline bilayer. The explicit water and ions are omitted for clarity. The images were created with visual molecular dynamics (VMD). (Reprinted with permission from Ref 42. Copyright 2006 Americal Chemical Society).
Confocal scanning microscopy of porcine skin treated with QD 565 for 8 h. (a‐c) QD‐PEG; (d‐f) QD‐PEG‐NH2; (g‐i) QD‐COOH. DIC channel (a, d, g) provides an unobstructed view of the skin layers. Confocal‐DIC overlay with the green QD fluorescence channel (b, e, h) shows QD localization within the epidermis or dermis (arrows). Fluorescence intensity scan of the QD emission (c, f, i). QD 565 are localized in the epidermal (PEG and COOH coatings) or dermal (NH2 coating) layers by 8 h. Scale bars equal 50 µm. (Figure revised with permission from Ref 47. Copyright 2006 Oxford Press).
works at the interface of biotechnology and materials science. His lab is researching many topics, such as investigating the mechanism of release from polymeric delivery systems with concomitant microstructural analysis and mathematical modeling; studying applications of these systems including the development of effective long-term delivery systems for insulin, anti-cancer drugs, growth factors, gene therapy agents and vaccines; developing controlled release systems that can be magnetically, ultrasonically, or enzymatically triggered to increase release rates; synthesizing new biodegradable polymeric delivery systems which will ultimately be absorbed by the body; creating new approaches for delivering drugs such as proteins and genes across complex barriers such as the blood-brain barrier, the intestine, the lung and the skin; stem cell research including controlling growth and differentiation; and creating new biomaterials with shape memory or surface switching properties.