Prolonged systemic delivery of streptokinase using liposome

Area of Science:

• Pharmacology
• Biotechnology
• Drug Delivery

Background:

• Streptokinase is a thrombolytic agent used to treat blood clots.
• Short biological half-life limits the efficacy of conventional streptokinase administration.
• Liposomes offer a potential strategy for improving drug pharmacokinetics.

Purpose of the Study:

• To develop and evaluate streptokinase-bearing liposomes to prolong the biological half-life of streptokinase.
• To enhance the circulation time and potential thrombolytic activity of streptokinase.

Main Methods:

• Streptokinase-bearing liposomes were prepared using distearoylphosphatidylcholine (DSPC), cholesterol, cholesterol-3-sulfate, and distearoylphosphatidyl ethanolamine-N-poly (ethylene glycol) 2000 (DSPE-PEG 2000) via a freeze-thawing method.
• Liposomes were administered intravenously to rats at a dosage of 15,000 IU/kg.
• Plasma streptokinase activity was measured using an amidolytic assay.
• Pharmacokinetic parameters, including half-life (T1/2) and area under the curve (AUCinfinity), were compared between liposomal streptokinase and free streptokinase.

Main Results:

• The incorporation of streptokinase into DSPC-PEG liposomes significantly increased its biological half-life (T1/2) by 16.3-fold.
• The area under the plasma concentration-time curve (AUCinfinity) for liposomal streptokinase was 6.1-fold higher than that of free streptokinase.
• These findings indicate enhanced circulation time of streptokinase within liposomes.

Conclusions:

• Streptokinase-bearing long-circulating liposomes effectively prolong the circulation time of streptokinase in the bloodstream.
• This enhanced circulation is expected to translate to longer-lasting thrombolytic activity compared to administration of streptokinase alone.
• Liposomal formulation represents a promising approach for improving streptokinase-based thrombolytic therapy.