Transport of poly amidoamine dendrimers across Madin–Darby canine kidney cells

Tajarobi, Farhad; El-Sayed, Mohamed; Rege, Bhagwant D.; Polli, James E.; Ghandehari, Hamid

doi:10.1016/s0378-5173(00)00679-7

Cited by 88 publications

(74 citation statements)

References 12 publications

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“…29,30 The influence of cationic PAMAM G4-NH 2 on Madin-Darby canine kidney (MDCK) cell monolayer integrity was performed by determining the permeability of mannitol across MDCK cells. 32 Results indicated that at 100 mg/ ml concentration of G4-NH 2 dendrimer, mannitol permeability increased by 9-fold, suggesting that cell integrity is compromised in the presence of G4. 32 Further evaluation of toxicity of PAMAM dendrimers was performed in other in vitro models such as fresh rat blood cells 48 and 3-D kidney organoid culture model.…”

Section: Toxicity Of Pamam Dendrimers In the Context Of Oral Deliverymentioning

confidence: 94%

“…32 Results indicated that at 100 mg/ ml concentration of G4-NH 2 dendrimer, mannitol permeability increased by 9-fold, suggesting that cell integrity is compromised in the presence of G4. 32 Further evaluation of toxicity of PAMAM dendrimers was performed in other in vitro models such as fresh rat blood cells 48 and 3-D kidney organoid culture model. 49 The release of hemoglobin after addition of PAMAM dendrimers G1.5-G9.5 to fresh rat blood cells (RBCs) and incubation at 37 C for 1 h was spectrophotometrically determined.…”

Section: Toxicity Of Pamam Dendrimers In the Context Of Oral Deliverymentioning

confidence: 94%

“…[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%

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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: Toxicity Of Pamam Dendrimers In the Context Of Oral Deliverymentioning

confidence: 94%

Section: Toxicity Of Pamam Dendrimers In the Context Of Oral Deliverymentioning

confidence: 94%

Section: Pamam Dendrimer Interaction With Tight Junctionsmentioning

confidence: 99%

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Poly(amido amine) dendrimers in oral delivery

Yellepeddi

Ghandehari

2016

Tissue Barriers

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“…These results are in opposition to those observed in cell culture, where there is a directly proportional relationship between the generation and the toxicity of the dendrimer. The observed difference could be due to the fact that, in cell culture, the cationic molecules bind to the cell membrane that has negative charge and destabilize it, leading to cell lysis (Lee and Larson 2008;Tajarobi et al 2001). It has been shown that positively charged dendrimers form pores in the cell membrane and the efficiency of this depends on the size of the nanoparticle, which explains that the higher the generation, the higher the toxicity (Lee and Larson 2008).…”

Section: Dendrimersmentioning

confidence: 99%

Relation between biophysical properties of nanostructures and their toxicity on zebrafish

et al. 2017

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In recent years, the use of commercial nanoparticles in different industry and health fields has increased exponentially. However, the uncontrolled application of nanoparticles might present a potential risk to the environment and health. Toxicity of these nanoparticles is usually evaluated by a fast screening assay in zebrafish (Danio rerio). The use of this vertebrate animal model has grown due to its small size, great adaptability, high fertilization rate and fast external development of transparent embryos. In this review, we describe the toxicity of different micro-and nanoparticles (carbon nanotubes, dendrimers, emulsions, liposomes, metal nanoparticles, and solid lipid nanoparticles) associated to their biophysical properties using this model. The main biophysical properties studied are size, charge and surface potential due to their impact on the environment and health effects. The review also discusses the correlation of the effects of the different nanoparticles on zebrafish. Special focus is made on morphological abnormalities, altered development and abnormal behavior. The last part of the review debates changes that should be made in future directions in order to improve the use of the zebrafish model to assess nanotoxicity.

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“…[11][12][13][14] Although the mechanism explaining generational effects is still unclear, higher generation dendrimers have been observed to cause nanoscale holes in the lipid bilayer, resulting in more toxicity while other authors have found that increasing generation attenuates toxicity; [13][14][15] especially for very high generation dendrimers, perhaps due to conformational changes. 11,[16][17][18] Regardless of dendrimer generation, some cationic dendrimers have been shown to interact with negatively charged cell membranes. 19 An increasing number of studies in diverse cell lines have shown that exposure to cationic dendrimers results in cell membrane permeability, cellular lysis, and cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

Pryor¹,

Harper²,

Harper³

2014

IJN

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Dendrimers are well-defined, polymeric nanomaterials currently being investigated for biomedical applications such as medical imaging, gene therapy, and tissue targeted therapy. Initially, higher generation (size) dendrimers were of interest because of their drug carrying capacity. However, increased generation was associated with increased toxicity. The majority of studies exploring dendrimer toxicity have focused on a small range of materials using cell culture methods, with few studies investigating the toxicity across a wide range of materials in vivo. The objective of the present study was to investigate the role of surface charge and generation in dendrimer toxicity using embryonic zebrafish ( Danio rerio ) as a model vertebrate. Due to the generational and charge effects observed at the cellular level, higher generation cationic dendrimers were hypothesized to be more toxic than lower generation anionic or neutral dendrimers with the same core composition. Polyamidoamine (PAMAM) dendrimers elicited significant morbidity and mortality as generation was decreased. No significant adverse effects were observed from the suite of thiophosphoryl dendrimers studied. Exposure to ≥50 ppm cationic PAMAM dendrimers G3-amine, G4-amine, G5-amine, and G6-amine caused 100% mortality by 24 hours post-fertilization. Cationic PAMAM G6-amine at 250 ppm was found to be statistically more toxic than both neutral PAMAM G6-amidoethanol and anionic PAMAM G6-succinamic acid at the same concentration. The toxicity observed within the suite of varying dendrimers provides evidence that surface charge may be the best indicator of dendrimer toxicity. Dendrimer class and generation are other potential contributors to the toxicity of dendrimers. Further studies are required to better understand the relative role each plays in driving the toxicity of dendrimers. To the best of our knowledge, this is the first in vivo study to address such a broad range of dendrimers.

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Transport of poly amidoamine dendrimers across Madin–Darby canine kidney cells

Cited by 88 publications

References 12 publications

Poly(amido amine) dendrimers in oral delivery

Poly(amido amine) dendrimers in oral delivery

Relation between biophysical properties of nanostructures and their toxicity on zebrafish

Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

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