Transepithelial transport of poly(amidoamine) dendrimers across Caco-2 cell monolayers

El-Sayed, Mohamed; Ginski, Mark; Rhodes, Christopher A.; Ghandehari, Hamidreza

doi:10.1016/s0168-3659(02)00087-1

Cited by 239 publications

(203 citation statements)

References 19 publications

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“…[28][29][30][31][32] The detailed mechanistic studies were then performed to elucidate the interaction of PAMAM dendrimers with the tight junction of the epithelium. Tight junctions are protein complexes that include occludin, claudins, junctional-associated membrane protein (JAM), and zonula occludens proteins (ZO-1, ZO-2).…”

Section: Pamam Dendrimer Interaction With Tight Junctionsmentioning

confidence: 99%

Poly(amido amine) dendrimers in oral delivery

Yellepeddi

Ghandehari

2016

Tissue Barriers

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Poly(amidoamine) (PAMAM) dendrimers have been extensively investigated for oral delivery applications due to their ability to translocate across the gastrointestinal epithelium. In this Review, we highlight recent advances in the evaluation of PAMAM dendrimers as oral drug delivery carriers. Specifically, toxicity, mechanisms of transepithelial transport, models of the intestinal epithelial barrier including isolated human intestinal tissue model, detection of dendrimers, and surface modification are discussed. We also highlight evaluation of various PAMAM dendrimer-drug conjugates for their ability to transport across gastrointestinal epithelium for improved oral bioavailability. In addition, current challenges and future trends for clinical translation of PAMAM dendrimers as carriers for oral delivery are discussed.

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Section: Pamam Dendrimer Interaction With Tight Junctionsmentioning

confidence: 99%

Poly(amido amine) dendrimers in oral delivery

Yellepeddi

Ghandehari

2016

Tissue Barriers

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“…Studies from our laboratory (8)(9)(10) and others (11)(12)(13) point to the potential of PAMAM dendrimers in oral drug delivery. A diverse array of in-vitro studies have demonstrated the influence of generation, surface charge and hydrophobicity on the transepithelial transport of PAMAM dendrimers (10,(14)(15)(16). PAMAM dendrimers with positive surface charge at physiological pH were found to permeate across the intestinal barrier to a higher extent compared to their neutral and negatively charged counterparts.…”

Section: Introductionmentioning

confidence: 99%

Potential Oral Delivery of 7-Ethyl-10-Hydroxy-Camptothecin (SN-38) using Poly(amidoamine) Dendrimers

2008

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Purpose-To investigate potential application of poly(amidoamine) (PAMAM) dendrimers for improving the delivery of SN-38.Methods-Complexes of SN-38 with generation 4 amine terminated PAMAM dendrimers were synthesized with varying amounts of drug. Stability of the complexes as well as influence of complexation on permeability across and cellular uptake by Caco-2 cells was evaluated.Results-The complexes were stable at pH 7.4 and drug was released at pH 5. A tenfold increase in permeability and more than hundredfold increase in cellular uptake of the complexes with respect to free SN-38 was observed.Conclusions-Studies suggest that complexation with PAMAM dendrimers has the potential to improve the oral bioavailability of SN-38.

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“…Anionic PAMAM dendrimers exhibited rapid transport rates across everted rat intestine as compared to positively charged dendrimers (El-Sayed et al 2002;Kitchens et al 2006). Dr. D'Emanuele's research group has been extensively working on increasing the transcellular permeability of the PAMAM dendrimers by surface modification with fatty acid molecules (Jevaprasesphant et al 2003) and preparation of dendrimer prodrugs for some poorly water soluble p-glycoprotein substrates (D'Emanuele et al 2004;Najlah and D'Emanuele 2007).…”

Section: Discussionmentioning

confidence: 99%

“…The higher BA permeabilities of the dendrimers over AB permeability may be attributed to differences in tight junctional structure (Noach et al 1993;El-Sayed et al 2002;Schierack et al 2006).…”

Section: Discussionmentioning

confidence: 99%

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Transport of Surface Engineered Polyamidoamine (PAMAM) Dendrimers Across IPEC-J2 Cell Monolayers

Pisal¹,

Yellepeddi²,

Kumar³

et al. 2008

Drug Delivery

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The aim of our study was to prepare arginine-and ornithineconjugated Polyamidoamine (PAMAM) dendrimers and study their permeability across IPEC-J2 cell monolayers, a new intestinal cell line model for drug absorption studies. Arginine and ornithine were conjugated to the amine terminals of the PAMAM G4 dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to-apical (BA) apparent permeability coefficients (P app ) for the PAMAM dendrimers increased by conjugating the dendrimers with both of these polyamines. The enhancement in permeability was dependent on the dendrimer concentration and duration of incubation. Correlation between monolayer permeability and the decrease in transepithelial electrical resistance (TEER) with the PAMAM dendrimers and the polyamine-conjugated dendrimers suggests that paracellular transport is one of the mechanisms of transport across the epithelial cells. Cytotoxicity of these surface-modified dendrimers was evaluated in IPEC-J2 cells by MTT (methylthiazoletetrazolium) assay. Arginine-conjugated dendrimers were insignificantly more toxic than PAMAM dendrimer as well as ornithine-conjugated dendrimers. Though investigations on the possible involvement of other transport mechanisms are in progress, results of the present study suggest the potential of dendrimer-polyamine conjugates as the carriers for antigen/drug delivery through the oral mucosa.

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Transepithelial transport of poly(amidoamine) dendrimers across Caco-2 cell monolayers

Cited by 239 publications

References 19 publications

Poly(amido amine) dendrimers in oral delivery

Poly(amido amine) dendrimers in oral delivery

Potential Oral Delivery of 7-Ethyl-10-Hydroxy-Camptothecin (SN-38) using Poly(amidoamine) Dendrimers

Transport of Surface Engineered Polyamidoamine (PAMAM) Dendrimers Across IPEC-J2 Cell Monolayers

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