Synthesis, nano-features, ex vivo anti-platelet aggregation and in vivo antithrombotic activities of poly-α,β-dl-aspartyl-l-arginine

Abstract

In the nanoscale assembly-based design of antithrombotic agents, poly-α,β-DL-aspartyl-L-arginine (MW: 20 741) was prepared from the thermal polycondensation of DL-aspartic acid and the amidation of polysuccimide with L-arginine. In the pH environments corresponding to the stomach (pH 1.2), intestinal tract (pH 7.6), blood and tissue fluids (pH 7.4) 4.8 × 10^{4,2,−4,−6,−8} nM of poly-α,β-DL-aspartyl-L-arginine assembled to form diverse nano-species. The sizes of the smallest nanoparticle, nanobell and nanomango were less than 100 nm. At the oral doses of 0.72, 1.44 and 2.89 μmol kg⁻¹, poly-α,β-DL-aspartyl-L-arginine dose-dependently inhibited the ex vivo platelet aggregation and the in vivo thrombosis of the treated rats. By assembling to form diverse nano-species, the absorption of oral poly-α,β-DL-aspartyl-L-arginine in the stomach and intestinal tract could be assisted.