Transepithelial Transport of PAMAM Dendrimers across Isolated Rat Jejunal Mucosae in Ussing Chambers
journal contributionposted on 17.12.2015, 03:40 by Dallin Hubbard, Hamidreza Ghandehari, David J. Brayden
Oral delivery remains a challenge for poorly permeable hydrophilic macromolecules. Poly(amido amine) (PAMAM) dendrimers have shown potential for their possible oral delivery. Transepithelial transport of carboxyl-terminated G3.5 and amine-terminated G4 PAMAM dendrimers was assessed using isolated rat jejunal mucosae mounted in Ussing chambers. The 1 mM FITC-labeled dendrimers were added to the apical side of mucosae. Apparent permeability coefficients (Papp) from the apical to the basolateral side were significantly increased for FITC when conjugated to G3.5 PAMAM dendrimer compared to FITC alone. Minimal signs of toxicity were observed when mucosae were exposed to both dendrimers with respect to transepithelial electrical resistance changes, carbachol-induced short circuit current stimulation, and histological changes. [14C]-mannitol fluxes were not altered in the presence of 1 mM dendrimers, suggesting that the paracellular pathway was not affected at this concentration in this model. These results give insight into the mechanism of PAMAM dendrimer transepithelial rat jejunal transport, as well as toxicological considerations important for oral drug delivery.
Read the peer-reviewed publication
Ussing chambersFITCTransepithelial TransportUssing ChambersOral deliveryPAMAM Dendrimerstoxicological considerationshistological changesapical sideG 3.5 PAMAM dendrimerbasolateral sideresistance changesrat jejunal mucosaeApparent permeability coefficientsPAMAM dendrimer transepithelial rat jejunal transportparacellular pathway1 mM dendrimersIsolated Rat Jejunal MucosaeMinimal signsdrug deliveryTransepithelial transport