TITANIUM NANOPARTICLES CONJUGATED WITH STREPTOKINASE AS A MODIFIED THROMBOLYTIC AGENT
Keywords:Titanium, Nanoparticles, Streptokinase and Thrombolytic
Objective: Blood clots are the main cause of death worldwide by stroke and myocardial infarction. Streptokinase a thrombolytic agent that is used in the treatment of circulatory disorders.
Methods: Titanium Nanoparticles was supplied from Changsha Santech Co. Its characterized were studied using (FT-IR, XRD, AFM, FE-SEM). Streptokinase at concentration 0.1 mg/ml was conjugated with Titanium nanoparticles using PH equal to 5.2 with continuous stirring. Formation of Streptokinase loading Titanium nanoparticles confirmed using FT-IR, Ninhydrine’s test and Bradford protein assay. Physicochemical Properties were studied in vitro. Thrombolytic activity in vitro was determined using d–dimer indicator and weight of blood clot after treatment as indicators of thrombolytic activity.
Results: Titanium nanoparticles show particle size at range 31 nm. The thrombolytic activity of streptokinase loading Titanium nanoparticles shows significant value in d-dimer and weight of blood clot compared with the control group and non-significant compared with an equivalent amount of streptokinase alone.
Conclusion: Titanium nanoparticles conjugated with streptokinase show high thrombolytic activity against blood clots in vitro.
2. Banerjee A, Chisti Y, Banerjee UC. Streptokinase-a clinically useful thrombolytic agent. Biotechnol Adv 2004;22:287-307.
3. Kunamneni A, Abdelghani TT, Ellaiah P. Streptokinase-the drug of choice for thrombolytic therapy. J Thromb Thrombolysis 2007;23:9-23.
4. Modaresi SM, Ejtemaei Mehr S, Faramarzi MA, Esmaeilzadeh Gharehdaghi E, Azarnia M, Modarressi MH, et al. Preparation and characterization of self-assembled chitosan nanoparticles for the sustained delivery of streptokinase: an in vivo study. Pharm Dev Technol 2014;19:593-7.
5. Yin ZF, Wu L, Yang HG, Su YH. Recent progress in biomedical applications of titanium dioxide. Phys Chem Chem Phys 2013;15:4844-58.
6. Chen Z, Wang Y, Zhuo L, Chen S, Zhao L, Luan X, et al. Effect of titanium dioxide nanoparticles on the cardiovascular system after oral administration. Toxicol Lett 2015;239:123-30.
7. Baharifar H, Tavoosidana G, Karimi R, Bidgoli SA, Ghanbari H, Faramarzi MA, et al. Optimization of self-assembled chitosan/streptokinase nanoparticles and evaluation of their cytotoxicity and thrombolytic activity. J Nanosci Nanotechnol 2015;15:10127-33.
8. Ayon AA, Cantu M, Chava K, Agrawal CM, Feldman MD, Johnson D, et al. Drug loading of nanoporous TiO2 films. Biomed Materials 2006;1:L11.
9. Karuppuchamy S, Jeong JM. Synthesis of nanoparticles of TiO2 by the simple aqueous route. J Oleo Sci 2006;55:263-6.
10. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-54.
11. Sedmak JJ, Grossberg SE. A rapid, sensitive, and versatile assay for protein using coomassie brilliant blue G250. Anal Biochem 1977;79:544-52.
12. Baharifar H, Amani A. Cytotoxicity of chitosan/streptokinase nanoparticles as a function of size: an artificial neural networks study. Nanomed: Nanotechnol Biol Med 2016;12:171-80.
13. Shamsi M, Zahedi P. On-chip preparation of streptokinase entrapped in chitosan nanoparticles used in thrombolytic therapy potentially. J Pharm Sci 2017;106:3623-30.
14. Kamal AM, Chowdhury KA, Shill LK, Hossain MR, Islam N, Anaytulla IA, et al. Phytochemical screening, the cytotoxic and thrombolytic activity of extract of brassica oleracea flower (cauliflower). Global J Pharmacol 2015;9:115-20.
15. Prasad S, Kashyap RS, Deopujari JY, Purohit HJ, Taori GM, Daginawala HF. Development of an in vitro model to study clot lysis activity of thrombolytic drugs. Thromb J 2006;4:14.
16. Kyrle PA, Eichinger S. Deep vein thrombosis. Lancet 2005;365:1163-74.
17. Elf JL, Strandberg K, Svensson PJ. Performance of two relatively new quantitative D-dimer assays (Innovance D-dimer and AxSYM D-dimer) for the exclusion of deep vein thrombosis. Thromb Res 2009;124:701-5.
18. Shi H, Magaye R, Castranova V, Zhao J. Titanium dioxide nanoparticles: a review of current toxicological data. Part Fibre Toxicol 2013;10:15.
19. Al-Taweel SS, Saud HR. New route for the synthesis of pure anatase TiO2 nanoparticles via ultrasound-assisted sol-gel method. J Chem Pharm Res 2016;8:620-6.
20. Swathi N, Sandhiya D, Rajeshkumar S, Lakshmi T. Green synthesis of titanium dioxide nanoparticles using cassia fistula and its antibacterial activity. Int J Res Pharm Sci 2019;10:856-60.
21. Marrese M, Guarino V, Ambrosio L. Atomic force microscopy: a powerful tool to address scaffold design in tissue engineering. J Functional Biomaterials 2017;8:7.
22. Hanawalt JD, Rinn HW, Frevel LK. Chemical analysis by X-ray diffraction. Industrial Engineering Chem Anal Edition 1938;10:457-512.
23. Baysal A, Kuznek C, Ozcan M. Starch coated titanium dioxide nanoparticles as a challenging sorbent to separate and preconcentrate some heavy metals using graphite furnace atomic absorption spectrometry. Ind Eng Chem Anal Ed 2018;98:45-55.
24. Laperriere LE, Yruegas S, Martin CD. Investigating the reactivity of 9-phenyl-9-borafluorene with NH, OH, PH, and SH bonds. Tetrahedron 2019;75:937-43.
25. Weisel JW, Litvinov RI. Fibrin formation, structure and properties. In: Fibrous Proteins: Structures and Mechanisms. Springer, Cham; 2017. p. 405-56.