Anti-angiogenic poly-L-lysine dendrimer binds heparin and neutralizes its activity

Publication date: 2012 Source:Results in Pharma Sciences, Volume 2 Author(s): Khuloud T. Al-Jamal , Wafa T. Al-Jamal , Kostas Kostarelos , John A. Turton , Alexander T. Florence The interaction between heparin, a polyanion, and a polycationic dendrimer with a glycine core and lysine branches Gly–Lys63(NH2)64 has been investigated. Complexation was assessed by transmission electron microscopy, size and zeta potential measurements, methylene blue spectroscopy, and measuring the anti-coagulant activity of heparin in vitro and in vivo. Complete association between the heparin and the dendrimer occurred a 1:1 mass ratio (2:1 molar ratio or +/−charge ratio) with formation of quasi-spherical complexes in the size range of 99–147nm with a negative zeta potential (−47mV). Heparin–dendrimer (dendriplex) formation led to a concentration-dependent neutralization of the anticoagulant activity of heparin in human plasma in vitro, with complete loss of activity at a 1:1 mass ratio. The anticoagulant activity of the dendriplexes in Sprague-Dawley rats was also evaluated after subcutaneous administration with uncomplexed heparin as a comparator. The in vivo anticoagulant activity of heparin in plasma, evaluated using an antifactor Xa assay, was abolished after complexation. Measurement of [3H]-heparin showed that both free heparin and dendriplexes were present in plasma and in organs. Such data confirmed stably the formation of dendriplexes, which could be essential in deve...
Source: Results in Pharma Sciences - Category: Drugs & Pharmacology Source Type: research