Transepithelial and endothelial transport of poly (amidoamine) dendrimers.
This article summarizes our efforts to evaluate the potential of poly (amidoamine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the permeability of a series of cationic PAMAM-NH2 (G0-G4) dendrimers across Caco-2 cell monolayers was evaluated as a function of dendrimer generation, concentration, and incubation time. The influence of dendrimer surface charge on the integrity, paracellular permeability, and viability of Caco-2 cell monolayers was monitored by measuring the transepithelial electrical resistance (TEER), 14C-mannitol permeability, and leakage of lactate dehydrogenase (LDH) enzyme, respectively. Microvascular extravasation of PAMAM-NH2 dendrimers in relation to their size, molecular weight, and molecular geometry is also discussed. Results of these studies show that transepithelial transport and microvascular extravasation of PAMAM dendrimers are dependent on their structural features including molecular size, molecular geometry, and surface chemistry. These results suggest that by optimizing the size and surface charge of PAMAM dendrimers, it is possible to develop oral delivery systems based on these carriers for targeted drug delivery.
Kitchens
Kelly M
KM
Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Baltimore, Maryland 21201-1075, USA.
El-Sayed
Mohamed E H
ME
Ghandehari
Hamidreza
H
D000818:Animals; D001693:Biological Transport, Active; D002196:Capillaries / Q000378:metabolism; D050091:Dendrimers / Q000493:pharmacokinetics*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D011073:Polyamines / Q000493:pharmacokinetics*
D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D011073:Polyamines