Delivery of tissue plasminogen activator and streptokinase magnetic nanoparticles to target vascular diseases

作者：Tadayon Ateke; Jamshidi Reza; Esmaeili Akbar

来源：International Journal of Pharmaceutics, 2015, 495(1): 428-438.

DOI：10.1016/j.ijpharm.2015.09.008

• Magnetic nanoparticles
• Thrombolysis
• Drug delivery
• Tissue plasminogen activator
• Streptokinase

Thrombolytic therapy for acute myocardial infarction standardly makes use of the medications streptokinase (SK) and tissue plasminogen activator (tPA). In this study, the potential of silica-coated magnetic nanoparticles (SiO2-MNPs) as nanocarriers clinical thrombolytic therapy was investigated. SiO2-MNPs for use in targeted therapeutic delivery of tPA and SK were prepared using a combined technique incorporating controlled precipitation and hydrothermal methods. Response surface methodology (RSM) was employed to evaluate the efficiency of the SiO2-MNPs. The production of SK secreted from Streptococcus equi was enhanced using random mutagenesis. The tPA and SK A were encapsulated by means of a silanizing agent with a surface rich in 3-aminopropyltrimethoxysilane layered around the SiO2-MNPs. Blood clot lysis assays and fibrin-containing agarose plates were used to carry out in vitro thrombolysis testing. The optimum conditions for producing MNPs were found to be at pH = 13 and at a temperature of 75 degrees C for 45 min. Culture conditions of 2.75% NaCl concentration at initial pH = 7.5 for 90 s under UV resulted in maximum SK activity. The tPA/SK-conjugated SiO2-MNPs (SiO2-MNP-tPA-SK) increased operating stability in whole blood and storage stability in a buffer by 92%. More effective thrombolysis using magnetic targeting was indicated by a 38% reduction in blood clot lysis time achieved with SiO2-MNP-tPA-SK compared to administering the SiO2-MNPs without guidance. The silica-coated magnetic nanocarriers developed in this study show potential for improved clinical thrombolytic therapy.

• 出版日期2015-11-10