In vitro and in vivo analysis of the antithrombotic and toxicological profile of new antiplatelets N-acylhydrazone derivatives and development of nanosystems: determination of novel NAH derivatives antiplatelet and nanotechnological approach.

摘要: Abstract Background Cardiovascular diseases are the most frequent cause of morbidity and mortality worldwide. Among important cardiovascular atherothrombosis venous thromboembolism that present platelet aggregation as a key event. Currently, commercial antiplatelet agents display several undesirable effects, which prompt search for new compounds with better therapeutic index, more efficient body distribution mechanism. Methods In this work we characterized in vivo vitro antithrombotic toxicological profiles novel N -substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides derivatives also comparing them aspirin. addition analyzed stability active compound after encapsulation PLGA or PCL nanoparticles release profile these nanosystems. Results The biological results revealed not only selective effect against arachidonic acid-induced mainly 2c, 2e 2 h but their on pulmonary animal model survival rates (e.g. 82%) than aspirin (33%). overall was determined by (MTT reduction tests, neutral red uptake kidney VERO cells hemolysis assays) (pulmonary embolism) assays pointed 2c promising derivative potential lead compound. By using nanoprecipitation technique loaded into showing controlled over 21 days according to our drug tests. Conclusion According is interesting further studies it showed best activity allowing nanoencapsulation process. Thus may assist determining therapy favorable pharmacokinetics treatment thrombotic disorders.