Molecular dynamics simulations in drug delivery research: Calcium chelation of G3.5 PAMAM dendrimers

Poly(amido amine) (PAMAM) dendrimers have been considered as possible delivery systems for anticancer drugs. One potential advantage of these carriers would be their use in oral formulations, which will require absorption in the intestinal lumen. This may require the opening of tight junctions which may be enabled by reducing the Ca²⁺ concentration in the intestinal lumen, which has been shown as an absorption mechanism for EDTA (ethylenediaminetetraacetic acid). Using molecular dynamics simulations, we show that the G3.5 PAMAM dendrimers are able to chelate Ca²⁺ at similar proportions to EDTA, providing support to the hypothesis that oral formulations of PAMAM dendrimers could use this high chelating efficiency as a potential mechanism for permeating the tight junctions of the intestines if other formulation barriers could be overcome.