Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 57, Issue 15, Pages 2163-2176Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.addr.2005.09.013
Keywords
oral drug delivery; water-soluble polymers; poly (amidoamine) dendrimers; PAMAM; Caco-2 cells; endothelial barrier; microvascular extravasation; intravital microscopy
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Funding
- NIGMS NIH HHS [GM67278-01] Funding Source: Medline
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This article surninarizes our efforts to evaluate the potential of poly (amidoaminc) (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 nionolayers was evaluated as a function of dendrimer generation, concentration, and incubation time. The influence of dendrimer surface charge on the integrity, paracellular penneability, and viability of Caco-2 cell monolayers was monitored by measuring the transepithelial electrical resistance (TEER), C-14-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. (c) 2005 Elsevier B.V. All rights reserved.
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