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.
Department of Pharmacy, Uppsala University, Box 580-S-751 23, Uppsala, Sweden.
F
F
Tajarobi
M
M
El-Sayed
B D
BD
Rege
J E
JE
Polli
H
H
Ghandehari
D000818:Animals; D001672:Biocompatible Materials; D002417:Cattle; D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D050091:Dendrimers; D005456:Fluorescent Dyes; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D011073:Polyamines / Q000493:pharmacokinetics*
D001672:Biocompatible Materials; D050091:Dendrimers; D005456:Fluorescent Dyes; C104700:PAMAM Starburst; D011073:Polyamines