title: Delivery of tissue plasminogen activator and streptokinase magnetic nanoparticles to target vascular diseases.
abstract: 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°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.
authors.affiliation: Faculty of New Sciences and Technology, Semnan University, Semnan, Iran.
authors.forename: Ateke
authors.initials: A
authors.lastname: Tadayon
authors.affiliation: Faculty of New Sciences and Technology, Semnan University, Semnan, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Jamshidi
authors.affiliation: Department of Chemical Engineering, North Tehran Branch, Islamic Azad University, PO Box 19585/936 Tehran, Iran. Electronic address: akbaresmaeili@yahoo.com.
authors.forename: Akbar
authors.initials: A
authors.lastname: Esmaeili
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011437:Propylamines / Q000737:chemistry; D012821:Silanes / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D018502:Streptococcus equi / Q000201:enzymology / Q000254:growth & development; D013300:Streptokinase / Q000008:administration & dosage* / Q000494:pharmacology; D013499:Surface Properties; D013696:Temperature; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000494:pharmacology; D014652:Vascular Diseases / Q000188:drug therapy*
chemical_list: D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D011437:Propylamines; D012821:Silanes; C088294:3-aminopropyltrimethoxysilane; D012822:Silicon Dioxide; D013300:Streptokinase; D010959:Tissue Plasminogen Activator
keywords: Drug delivery; Magnetic nanoparticles; Streptokinase; Thrombolysis; Tissue plasminogen activator