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

Results in Pharma Sciences
Khuloud T Al-JamalAlexander T Florence

Abstract

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 99-147 nm with a negative zeta potential (-47 mV). 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 [(3)H]-heparin showed that both free heparin and dendriplexes were present in plasma and in organs. Such data confirmed stably the...Continue Reading

Citations

Jun 28, 2017·Organic & Biomolecular Chemistry·Ryan J WeissYitzhak Tor
Aug 14, 2012·Chemical Society Reviews·Sangram Keshari SamalPeter Dubruel
Jan 29, 2021·Drug Delivery and Translational Research·Alexander T Florence

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