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Wiwattanapatapee, Ruedeekorn; Carreño-Gómez, Begoña; Malik, Navid; Duncan, Ruth

doi:10.1023/a:1007587523543

Cited by 220 publications

(85 citation statements)

References 14 publications

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“…Full generation PAMAM dendrimers G4-G7, have previously been shown to have diameters of 4-8 nm [27], and similar to the results reported by Wiwattanapatapee et al [28], for G3.5 (4.0 nm) and G5.5 (6.7 nm) dendrimers, which are roughly in agreement with our results. In all cases, addition of cis-{Pt(NH 3 ) 2 } results in a decrease in the size of each dendrimer.…”

Section: Synthesis and Characterisation Of Drug-dendrimer Complexessupporting

confidence: 93%

Evaluation of anionic half generation 3.5–6.5 poly(amidoamine) dendrimers as delivery vehicles for the active component of the anticancer drug cisplatin

Kirkpatrick

Plumb

Sutcliffe

et al. 2011

Journal of Inorganic Biochemistry

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Title: Evaluation of anionic half generation 3.5-6.5 poly(amidoamine) dendrimers as delivery vehicles for the active component of the anticancer drug cisplatin Article Type: Regular Paper Keywords: cancer; platinum; PAMAM dendrimer; cisplatin; guanosine; cytotoxicity; diffusion NMR. Abstract: Aquated cisplatin was added to half-generation PAMAM dendrimers and the resultant complexes were purified by centrifuge. The drug-dendrimer complexes were then characterised by 1-D and diffusion 1H NMR y and ICP-AES. The amount of drug bound was found to increase in proportion with dendrimer size: G3.5, 22 cis-{Pt(NH3)2}molecules per dendrimer; G4.5, 37; G5.5, 54; and G6.5, 94, which represent only a fraction of the available binding sites on each dendrimer (68, 58, 42 and 37%, respectively). Drug release studies showed that some drug remains bound to the dendrimer even after prolonged incubation with 5'GMP at temperatures of 60 oC for over a week (percentage of drug released 18, 30, 35 and 63%, respectively). Attachment of the drug was found to decrease the radius of the dendrimers. Finally, the effect of the dendrimer on drug cytotoxicity was determined using in vitro assays with the A2780, A2780cis and A2780cp ovarian cancer cell lines. The free dendrimers display no cytotoxicity whilst the drug-dendrimer complexes showed moderate activity. In vivo activity was examined using an A2780 tumour xenograft. Cisplatin, at its maximum tolerated dose of 6 mg/kg, reduced tumour size by 33% compared to an untreated control group. The G6.5 cisplatin-dendrimer complex was administered at two doses (6 and 8 mg/kg equivalent of cisplatin). Both were well tolerated by the mice. The lower dose displayed comparable activity to cisplatin with a tumour volume reduction of 32%, but the higher dose was significantly more active than free cisplatin with a tumour reduction of 45%. We have revised the manuscript taking into account all your listed corrections and stylistic requirements.As siDNA and PBS were used only once in the manuscript we have now written these in full and not used them as abbreviations.For simplicity, we have made figure 5 just black and white and have changed the figure caption to reflect this. G4.5, 37; G5.5, 54; and G6.5, 94, which represent only a fraction of the available binding sites on each dendrimer (68, 58, 42 and 37%, respectively). Drug release studies showed that some drug remains bound to the dendrimer even after prolonged incubation with 5'GMP at temperatures of 60 o C for over a week (percentage of drug released 18, 30, 35 and 63%, respectively). Attachment of the drug was found to decrease the radius of the dendrimers. Finally, the effect of the dendrimer on drug cytotoxicity was determined using in vitro assays with the A2780, A2780cis and A2780cp ovarian cancer cell lines. The free dendrimers display no cytotoxicity whilst the drug-dendrimer complexes showed moderate activity. In vivo activity was examined using an A2780 tumour xenograft. Cisplatin, at its maximum tolerated dose of 6 mg/kg, reduced tu...

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Section: Synthesis and Characterisation Of Drug-dendrimer Complexessupporting

confidence: 93%

Evaluation of anionic half generation 3.5–6.5 poly(amidoamine) dendrimers as delivery vehicles for the active component of the anticancer drug cisplatin

Kirkpatrick

Plumb

Sutcliffe

et al. 2011

Journal of Inorganic Biochemistry

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“…Conversely, anionic dendrimers showed greater serosal transfer rates than their tissue uptake in the same model. 28 This study confirmed the results from Caco-2 monolayer studies that PAMAM dendrimer's generation and surface charge influence their transepithelial transport.…”

Section: Translocation Of Pamam Dendrimers Across Isolated Intestinalsupporting

confidence: 88%

“…28 The results have shown that cationic PAMAM dendrimers exhibited greater tissue uptake than their serosal transfer rates across everted rat intestinal sacs at each time point. Conversely, anionic dendrimers showed greater serosal transfer rates than their tissue uptake in the same model.…”

Section: Translocation Of Pamam Dendrimers Across Isolated Intestinalmentioning

confidence: 87%

“…[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%

“…28,[43][44][45][46] In vivo models in comparison to Caco-2 cell monolayers comprise mucus layers, supportive mixed cell populations, and basement membrane. Furthermore, these models allow the comparison of differences in the segmental transport throughout different regions of the GI tract.…”

Section: Translocation Of Pamam Dendrimers Across Isolated Intestinalmentioning

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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