Synthesis, nanofeatures, in vitro thrombus lysis activity and in vivo thrombolytic activity of poly-alpha,beta-aspartyl-L-alanine.

Applying nanoscale assembly to the design of a thrombolytic agent. poly-alpha,beta-DL-aspartyl-L-alanine (molecular weight: 15726 atomic mass units) from the thermal polycondensation of DL-aspartic acid and the amidation of polysuccimide with L-alanine. The correlation of concentration and pH with nanofeatures, the correlation of concentration with in vitro thrombus lysis activity, the correlation of dose with the in vivo thrombolytic activity and the correlation of the dose with nanofeatures are all explained in this article. Poly-alpha,beta-DL-aspartyl-L-alanine was concentration- (6.4 x 10(4,2,-4,-6,-8,-10,-12) nM) and pH-dependently (pH 1.2, 7.4 and 7.6) assembled to various nanospecies, exhibited concentration-dependent (4, 8 and 16 microM) lysis action in vitro and dose-dependent (5, 0.5 and 0.05 micromol/kg) thrombolytic action in vivo. Upon entering the stomach, intestinal tract, blood and tissue fluids, poly-alpha,beta-DL-aspartyl-L-alanine assembled to small nanoparticles or nanoblocks to escape the entrapment by macrophages and exhibited desirable thrombolytic action.