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dc.contributor.authorNajlah, Mohammaden
dc.contributor.authorFreeman, Sallyen
dc.contributor.authorKhoder, Mouhamaden
dc.contributor.authorAttwood, Daviden
dc.contributor.authorD’Emanuele, Antonyen
dc.date.accessioned2017-10-10T09:28:39Z
dc.date.available2017-10-10T09:28:39Z
dc.date.issued2017-10-04
dc.identifier.citationNajlah, M. et al. (2017) In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates. Molecules, 22 (10), 1661en
dc.identifier.urihttp://hdl.handle.net/2086/14588
dc.descriptionopen access articleen
dc.description.abstractThe present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM) dendrimers as drug carriers of naproxen (NAP), a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio via a diethylene glycol linker. A lauroyl chain (L), a lipophilic permeability enhancer, was attached to G3 and G0 prodrugs. The G3 and G0 conjugates were more hydrophilic than naproxen as evaluated by the measurement of partitioning between 1-octanol and a phosphate buffer at pH 7.4 and pH 1.2. The unmodified surface PAMAM-NAP conjugates showed significant solubility enhancements of NAP at pH 1.2; however, with the number of NAP conjugated to G3, this was limited to 10 molecules. The lactate dehydrogenase (LDH) assay indicated that the G3 dendrimer conjugates had a concentration dependent toxicity towards Caco-2 cells. Attaching naproxen to the surface of the dendrimer increased the IC50 of the resulting prodrugs towards Caco-2 cells. The lauroyl G3 conjugates showed the highest toxicity amongst the PAMAM dendrimer conjugates investigated and were significantly more toxic than the lauroyl-G0-naproxen conjugates. The permeability of naproxen across monolayers of Caco-2 cells was significantly increased by its conjugation to either G3 or G0 PAMAM dendrimers. Lauroyl-G0 conjugates displayed considerably lower cytotoxicity than G3 conjugates and may be preferable for use as a drug carrier for low soluble drugs such as naproxen.en
dc.language.isoenen
dc.publisherMDPIen
dc.subjectPAMAM dendrimersen
dc.subjecttransepithelial transporten
dc.subjectCaco-2 cellsen
dc.subjectdendrimer prodrugsen
dc.subjectoral drug deliveryen
dc.titleIn Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugatesen
dc.typeArticleen
dc.identifier.doihttp://dx.doi.org/10.3390/molecules22101661
dc.peerreviewedYesen
dc.funderN/Aen
dc.projectidN/Aen
dc.cclicenceCC BYen
dc.date.acceptance2017-10-04en
dc.exception.reasonopen access articleen


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