Synthesis, nanofeatures, in vitro thrombus lysis activity and in vivo thrombolytic activity of poly-alpha,beta-aspartyl-L-alanine.
OBJECTIVE
Applying nanoscale assembly to the design of a thrombolytic agent.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Gui
Lin
L
College of Pharmaceutical Sciences, Capital Medical University, Beijing, 100069, PR China.
Zhao
Ming
M
Wang
Yinye
Y
Qin
Yang
Y
Liu
Jiangyuan
J
Peng
Shiqi
S
D000818:Animals; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000188:drug therapy*
D005343:Fibrinolytic Agents; D011506:Proteins; C553661:poly-alpha,beta-aspartyl-alanine