Hamid Ghandehari

Transport mechanism(s) of poly (amidoamine) dendrimers across Caco-2 cell monolayers.

The objective of this research was to investigate the mechanism(s) of transport of generation 2 (G2) poly (amidoamine) dendrimers across Caco-2 cell monolayers. The contribution of an energy-dependent process such as adsorptive endocytosis was investigated by determining G2 permeability at 4 and 37 degrees C. The contribution of P-gp efflux to transport was examined by determining the apical to basolateral (AB) and basolateral to apical (BA) permeability of 14C-paclitaxel in presence of G2, and by determining AB and BA permeability of G2 in presence of paclitaxel. The permeability of G2 and 14C-mannitol was investigated in the presence of palmitoyl carnitine to determine the contribution of the paracellular pathway. Permeability of G2 at 4 degrees C was significantly (P<0.05) lower than that observed at 37 degrees C. AB and BA permeability of 14C-paclitaxel did not change in the presence of G2. AB and BA permeability of G2 did not change in the presence of paclitaxel. The permeability of G2 and 14C-mannitol increased significantly (P<0.05) in the presence of palmitoyl carnitine, and in addition, 14C-mannitol permeability was increased in presence of G2. The permeability of G2 across Caco-2 cell monolayers appears to involve a combination of paracellular transport and an energy-dependent process, possibly adsorptive endocytosis. G2 dendrimers do not appear to be substrates for the P-gp efflux system.

Transport of poly amidoamine dendrimers across Madin-Darby canine kidney cells

The objective of this study was to determine the permeability of a series of poly amidoamine (PAMAM) dendrimers of generations 0-4 (G0-G4) across MDCK (Madin-Darby Canine Kidney) cell line. PAMAM dendrimers with incremental increase in size and molecular weight were labeled by fluorescein isothiocyanate (FITC) and the least polydisperse fractions were collected by size exclusion chromatography. MDCK cells were grown on Transwell filters for four days. The conjugates were detected by HPLC equipped with fluorescence detector. The permeability of the dendrimers across MDCK cells was determined in the apical to basolateral direction. The rank-order permeability of the PAMAM dendrimers was G4 >> G1 approximately G0 > G3 > G2. The permeability of mannitol in the presence of G4 increased by nine-fold. Results suggest that the transepithelial transport of PAMAM dendrimers is effected by both the polymer size, and the modulation of the cell membrane by the cationic dendrimers.

New technology and clinical applications of nanomedicine: highlights of the second annual meeting of the American Academy of Nanomedicine (Part I).

Abstract The Second Annual Meeting of the American Academy of Nanomedicine (AANM) was held at the National Acadmy of Science Building in Washinton, DC, September 9–10, 2006. The program included two Nobel Prize Laureate Lectures, two Keynote Lectures, and 123 invited outstanding State-in-Art lectures presenting in 23 special concurrent symposia. In addition, there were 22 poster presentations in the meeting addressing different areas in nanomedicine research. All of the presenters at the meeting are outstanding investigators and researchers in the field. The Second Annual Meeting of the AANM was a great success. The meeting provides investigators from different world areas a forum and an opportunity for discussion. We believe that nanomedicine research will develop rapidly in the future. The AANM invites basic and clinical researchers from the world to join this exciting research.

MP09-05 SILK-ELASTINLIKE POLYMERS ENHANCE THE ANTI-INFLAMMATORY AND ANALGESIC PROPERTIES OF SEMISYNTHETIC GLYCOSAMINOGLYCANS

Semisynthetic Glycosaminoglycans M. Martin Jensen1,2, Wanjian Jia2,3, Austin J. Schults3, Kyle J. Isaacson1,2, Douglas Steinhauff1,2, Bryant Green1,2, Marcelo Correa1,2, Jeremiah A. Alt4, Joseph Cappello4, Hamid Ghandehari1,2,5, Siam Oottamasathien2,3,6,7 1Department of Bioengineering, University of Utah 2Utah Center for Nanomedicine, Nano Institute of Utah 3Department of Medicinal Chemistry, University of Utah 4Department of Surgery, University of Utah School of Medicine 5Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah 6Department of Surgery and Division of Pediatric Urology, Primary Children’s Medical Center, Salt Lake City, Utah, USA 7Department of Pediatric Surgery and Division of Pediatric Urology, Massachusetts General Hospital for Children/Harvard Medical School, Boston, MA, USA