Background : Diabetes mellitus (DM), a complex metabolic disorder associated with multiple pathological changes with heightened incidence of macrovascular complications resulting in increased cardiac vascular complications. Multiple factors are involved in the expansion of type II DM those liked with atherothrombosis such as inflammation, impaired fibrinolysis, heper-coagulation and endothelial dysfunction to name few. Principal perturbation viz., insulin resistance, hyperglycemia, adhesion molecule over-expression coagulation cascade activation and increased clot formation are also related to DM. In this study, we tried to scrutinize the nano-formulation of crocetin in preventing prothrombosis associated with DM. 

Methods : Nanoparticulate system for crocetin (CT-PLGA) was developed via using the ultra-sonication technique and influential formulation parameters were systematically optimized via Box-Behnken design to acquire quality range desired nano size compounds. Invitro fibrinolytic was performed carried with Streptozotocin (STZ) (55 mg/kg) induce he type II DM in rat model system. Rats were divided into different group and received the CT-PLGA treatment for 4 weeks. Finally, the levels of coagulation biomarkers like activate partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen along with pro-inflammatory cytokines and inflammatory mediator. 

Results : CT-PLGA nano-paticulates exhibited the average particle size of 187 nmwith poly-dispersity index 0.19, drug loading capacity >91%, eta potential <20 mV and sustained invitro 95% drug release after 48 h. CT-PLGA significantly (<0.001) reduced the blood glucose level (67%) and increase plasma insulin (54%) level, respectively. CT-PLGA down-regulated the cholesterol (34%), triglycerides (26%), IL-6 (22%), TNF-α (31%) and up-regulation of NO (48%) and aPPT (32%) as comparison to STZ induced DM rats. Moreover, CT-PLGA successfully reduced the platelet count and fibrinogen. The histopatology study of heart exhibited the less thickness of intercalated disc.

Conclusions : We can conclude that CT-PLGA treatment altered the biomarkers linked to the expansion of thrombosis and may also delay the thrombogensis associated to type II DM via altering the hypercoagulation and inflammation.