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1H NMR spectroscopy was used to analyze the interactions between poly(amidoamine) (PAMAM) Starburst dendrimers (SBDs) 1–4 and several biologically important guests (pyridine, quinoline, quinazoline, nicotine and trimethadione). Association constants obtained from changes in the chemical shifts of the amide protons in the host indicate two different interaction sites inside and on the periphery of the dendrimer. Binding at the inner site is inhibited in the ester‐terminated dendrimers. Copyright © 1998 John Wiley & Sons, Ltd.

The polarity and accessibility to the interior of several dendrimers using phenanthrene, anthracene and tetrabenzonaphtalene as probe molecules have been investigated. In addition the prospective application of the dendrimers as drug carriers was evaluated by incorporating 5(6)-methylbenzo[1,2-c]1,2,5-oxadiazole N 1 -oxide] (1) and 2 0 -(benzo[1,2-c] 1,2,5-oxadiazol-5(6)-yl(N 1 -oxide) methylidene]-1-methoxy methane hydrazide (2). These compounds have antichagasic therapeutic activity but very low water solubility, which limits their application. Polypropylene imine dendrimers with amine terminal groups (DAB-16AT and DAB-32AT) and polyamide amine (PAMAM) dendrimers with carboxylate terminal groups (PAMAM-32CT), with amine terminal groups, (PAMAM-8AT and PAMAM-32AT) and with hydroxyl terminal groups (PAMAM-32OHT) were chosen for this study. Approximately one molecule of phenanthrene or anthracene was encapsulated in PAMAM-32CT, PAMAM-32AT, PAMAM-32OHT and DAB-32AT dendrimers. However, slight encapsulation was observed working with PAMAM-8AT and DAB-16AT. The studies with tetrabenzonaphtalene show that the guest molecule might only be partially caged within the dendrimer host. However, for relatively insoluble solutes the efficiency to encapsulate can be dictated by the saturation in the aqueous phase besides the dendrimer capacity to dissolve it. These dendrimers are also able to encapsulate and consequently solubilize 1 and 2 oxadiazol. However, PAMAM dendrimers are better for encapsulation and retention due to guest-host specific interactions. These interactions can be diminished by lowering the pH to allow a controlled deliverance of the drug.

In the present work, we investigated a first generation of a new dendrimer as candidate for intravenous (iv) administration of a therapeutic compound (2′‐(benzo[1,2‐c] 1,2,5‐oxadiazol‐5(6)‐yl (N‐1‐oxide) methylidene]‐1‐methoxy methane hydrazide). This compound presents antichagasic activity but low water solubility. Guest–host specific interactions results in good drug solubilization. These interactions can be controlled by varying the solution pH, allowing drug deliverance. Interaction between dendrimer and human serum albumin (HSA), and the hemolytic potential of dendrimer were evaluated. The dendrimer does not interact with blood proteins, is not hemolytic, and does not produce damage in the cellular membrane. The results demonstrate that the new dendritic structure could be an appropriate carrier for the novel antichagasic drug. Copyright © 2008 John Wiley & Sons, Ltd.

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