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Beware of phosphate: evidence of specific dendrimer–phosphate interactions

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Abstract

Dendrimers are extensively studied for drug delivery and catalysis, most of which are pH dependent. Phosphate buffer solutions (PBSs) are often used to adjust the pH. We have found that phosphate ions become incorporated into poly(amidoamine) (PAMAM) dendrimer molecules by forming H-bonds with tertiary nitrogens. We show that this specific interaction between H2PO4 and HPO42− ions and generation five PAMAM dendrimers causes a decrease in hydrodynamic size, disturbing the outcome of the size exclusion chromatography analysis. We monitored this interaction by 1H and 31P high resolution NMR, NMR-diffusiometry, pH-potentiometry and infrared spectroscopy. Failing to take into account this effect may lead to incorrect conclusions and misinterpreting interactions of PAMAM dendrimers with drug molecules and subsequently incorrect dosing. The phosphate salts of amino terminated generation five PAMAM dendrimers are stable for years when stored in the dark, even in dilute aqueous solutions, which has important implications for the shelf-life of dendrimer-based drug delivery systems.

Graphical abstract: Beware of phosphate: evidence of specific dendrimer–phosphate interactions

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Publication details

The article was received on 09 Feb 2017, accepted on 31 Mar 2017 and first published on 31 Mar 2017


Article type: Paper
DOI: 10.1039/C7CP00875A
Citation: Phys. Chem. Chem. Phys., 2017, Advance Article
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    Beware of phosphate: evidence of specific dendrimer–phosphate interactions

    M. Kéri, Z. Nagy, L. Novák, E. Szarvas, L. P. Balogh and I. Bányai, Phys. Chem. Chem. Phys., 2017, Advance Article , DOI: 10.1039/C7CP00875A

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