Development and characterization of highly selective target-sensitive liposomes for the delivery of streptokinase: in vitro/in vivo studies

Abstract

Streptokinase is one of the most commonly used thrombolytic agents for the treatment of thromboembolism. Short half-life of the streptokinase requires administration of higher dose which results in various side effects including systemic haemorrhage due to activation of systemic plasmin. To increase the selectivity of the streptokinase and hence to reduce side effects, various novel carriers have been developed. Among these carriers, liposomes have been emerged as versatile carrier. In the present study, highly selective target-sensitive liposomes were developed and evaluated by in vitro and in vivo studies. Prepared liposomes were found to release streptokinase in vitro following binding with activated platelets. Intravital microscopy studies in thrombosed murine model revealed higher accumulation of liposomes in the thrombus area. In vivo thrombolysis study was performed in the human clot inoculated rat model. Results of the study showed that target-sensitive liposomes dissolved 28.27 ± 1.56% thrombus as compared to 17.18 ± 1.23% of non-liposomal streptokinase. Further, it was also observed that target-sensitive liposomes reduced the clot dissolution time as compared to streptokinase solution. Studies concluded that developed liposomes might be pragmatic carriers for the treatment of thromboembolism.

Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis

“…In the context of thioether instability possibilities in vivo, our future studies will explore alternative strategies of bioconjugation, especially using copper-free click chemistry. In the context of drug loading efficacy, liposomal encapsulation of streptokinase (SK) has been reported previously by a few groups, with values ranging in 10–35% EE [60–63]. In our studies we have observed a range of ~20–45% EE for SK in liposomes, based on processing parameters [64].…”

Nanoparticle delivery of anticancer drugs overcomes multidrug resistance in breast cancer

“…Modified with selective ligands, liposome encapsulated drugs undergo targeted endocytosis and thus are not subject to active drug efflux by MDR transporters (Kapse-Mistry et al, 2014). Alternatively, higher temperature and lower pH in tumor tissue can be exploited by manufacturing temperature and pH-sensitive liposomes, which release drugs in target tissue in a temperature and pH-dependent manner (Qin et al, 2014;Vaidya et al, 2016).…”

VCAM-1 directed target-sensitive liposomes carrying CCR2 antagonists bind to activated endothelium and reduce adhesion and transmigration of monocytes

“…Previously, TSL obtained by stabilization of unsaturated DOPE into bilayers using antibodies or peptide derivatives of fatty acids (palmitic acid) were employed for the delivery of antiviral agents [12][13][14][26][27][28] or streptokinase. 29,30 We performed optimization studies by varying fractions of DOPA or the PEG-DSPE derivatives to establish the liposomes composition that best guarantee the stability of the targeted carrier system in the blood until they reach the molecular target on the surface of activated EC. Based Only one previous study investigated the effects of different amount of PEG-derived phospholipids on the activity of target-sensitive liposomes.…”