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    In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates

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    Date
    2017-10-04
    Author
    Najlah, Mohammad;
    Freeman, Sally;
    Khoder, Mouhamad;
    Attwood, David;
    D’Emanuele, Antony
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    Abstract
    The 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.
    Description
    open access article
    Citation : Najlah, M. et al. (2017) In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates. Molecules, 22 (10), 1661
    URI
    http://hdl.handle.net/2086/14588
    DOI
    http://dx.doi.org/10.3390/molecules22101661
    Peer Reviewed : Yes
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    • Leicester School of Pharmacy [1196]

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