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.

• Streptokinase
• target-sensitive liposomes
• targeting
• thrombolytic agents
• thrombus

Acknowledgements

Author B. Vaidya wants to acknowledge All India Council of Technical Education (AICTE), New Delhi, for providing funding in the form of National Doctoral Fellowship (NDF). Authors would like to acknowledge the help of Prof. S. C. Lakhotia, Department of Zoology, BHU, Varanasi, India, to conduct confocal laser scanning microscopy. Authors also want to acknowledge Sophisticated Analytical Instrumentation Facility (SAIF), Punjab University, Chandigarh, India, to perform TEM, FTIR, NMR and mass spectroscopy.

Declaration of interest

The research was supported in part by grants received by D. Dash from the Council of Scientific & Industrial Research (CSIR) and the Department of Science & Technology (DST), Government of India. Funding was also provided from the All India Council of Technical Education (AICTE), New Delhi, in the form of National Doctoral Fellowship (NDF). The authors report no declarations of interest.