Micro and Nanoparticles as Carriers for Streptokinase: A Mini-Review on Efficacy, Side Effects and Pharmacokinetics

Document Type : Review Paper

Author

1 Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran

2 Department of Advanced Technologies, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

10.22034/nmrj.2024.01.001

Abstract

Streptokinase is being successfully used as a thrombolytic agent for restoring the blood flow following thromboembolism and myocardial infarction. However, high immunogenicity of the drug has limited its use in clinics. To overcome this limitation, several approaches including PEGylation, use of polymeric particles and liposomes have been suggested. Here, an overview of options for encapsulating the streptokinase has been provided. The suggested options in the literature include PEGylation, polymeric nano/micro-capsules and liposomes. In each approach, efficacy, side effect(s) and pharmacokinetic profile of streptokinase has been evaluated. The data show that while efficacy of streptokinase does not appear to change importantly, side effects and pharmacokinetics have been improved.

Keywords

Main Subjects


‎2.‎ Zenych A, Fournier L, Chauvierre C. Nanomedicine progress in thrombolytic therapy. Biomaterials, ‎‎2020;258:120297.‎ https://doi.org/10.1016/j.biomaterials.2020.120297
‎3.‎ Banerjee A, Chisti Y, Banerjee U. Streptokinase-a clinically useful thrombolytic agent. ‎Biotechnology advances, 2004;22 (4):287-307.‎ https://doi.org/10.1016/j.biotechadv.2003.09.004
‎4.‎ Schellekens H, Jiskoot W. Immunogenicity of therapeutic proteins. Pharmaceutical biotechnology: ‎Springer; 2013:133-141.‎ https://doi.org/10.1007/978-1-4614-6486-0_6
‎5.‎ Elliott JM, Cross DB, Cederholm-Williams SA, White HD. Neutralizing antibodies to streptokinase ‎four years after intravenous thrombolytic therapy. The American journal of cardiology, 1993;71 ‎‎(8):640-645.‎ https://doi.org/10.1016/0002-9149(93)91003-Z
‎6.‎ Vaidya B, Agrawal G, Vyas SP. Functionalized carriers for the improved delivery of plasminogen ‎activators. International journal of pharmaceutics, 2012;424 (1-2):1-11.‎ https://doi.org/10.1016/j.ijpharm.2011.12.032
‎7.‎ Wu X-C, Ye R, Duan Y, Wong S-L. Engineering of plasmin-resistant forms of streptokinase and their ‎production in Bacillus subtilis: streptokinase with longer functional half-life. Applied and ‎environmental microbiology, 1998;64 (3):824-829.‎ https://doi.org/10.1128/AEM.64.3.824-829.1998
‎8.‎ Shi G-Y, Chang B-I, Su S-W, Young K-C, Wu D-H, Chang L-C, Tsai Y-S, Wu H-L. Preparation of a ‎novel streptokinase mutant with improved stability. Thrombosis and haemostasis, 1998;79 ‎‎(05):992-997.‎ https://doi.org/10.1055/s-0037-1615108
‎9.‎ Bandehpour M, Sharifnia Z, Mohajeri N, Taherkhani M, Koochaki A, Yarian F, Seyyed N, Shirvani R, ‎Pakzad P, Saadat H. Comparative study of the reactivity of natural and mutated streptokinase with ‎total antistreptokinase antibodies in human sera. Blood coagulation & fibrinolysis, 2012;23 ‎‎(8):734-738.‎ https://doi.org/10.1097/MBC.0b013e328358e87b
‎10.‎ Ojalvo A, Torrens I, Seralena A, de la Fuente J. Recombinant streptokinase with reduced ‎immunoreactivity. Thrombosis and Haemostasis: Fk Schattauer Verlag Gmbh Po Box 10 ‎‎45 43, Lenzhalde 3, D-70040 Stuttgart …; 1999:260-261.‎
‎11.‎ Akbar G, Zia M, Ahmad A, Arooj N, Nusrat S. Review on streptokinase with its antigenic ‎determinants and perspectives to develop its recombinant enzyme with minimum immunogenicity. ‎Journal of Innovative Sciences, 2020;6 (1):17-23.‎ https://doi.org/10.17582/journal.jis/2020/6.1.17.23
‎12.‎ Alinodehi NN, Sadeh S, Nezamiha FK, Keramati M, Hasanzadeh M, Mianroodi RA. Evaluation of ‎activity kinetic parameters of SK319cys, as a new cysteine variant of streptokinase: a comparative ‎study. Current Pharmaceutical Biotechnology, 2019;20 (1):76-83.‎ https://doi.org/10.2174/1389201020666190208155808
‎13.‎ Alinodehi NN, Behrooz H, Sabaei M, Nezamiha FK, Mianroodi RA. Multiple Mutations on α, β and γ ‎Domains of Streptokinase Lead to the Generation of Highly Efficient Cysteine Analogues with ‎Promising Features. Current Pharmaceutical Biotechnology, 2022.‎
‎14.‎ Alinodehi NN, Behrooz H, Sabaei M, Nezamiha FK, Mianroodi RA. Multiple Mutations on α, β and γ ‎Domains of Streptokinase Lead to the Generation of Highly Efficient Cysteine Analogues with ‎Promising Features. Current Pharmaceutical Biotechnology, 2023;24 (10):1326-1334.‎ https://doi.org/10.2174/1389201024666221124151623
‎15.‎ Kumar L, Verma S, Vaidya B. Liposomes for the delivery of streptokinase. Therapeutic delivery, ‎‎2017;8 (10):855-866.‎ https://doi.org/10.4155/tde-2017-0026
‎16.‎ Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nature reviews Drug discovery, ‎‎2003;2 (3):214-221.‎ https://doi.org/10.1038/nrd1033
‎17.‎ Leach JK, Patterson E, O'Rear E. Distributed intraclot thrombolysis: mechanism of accelerated ‎thrombolysis with encapsulated plasminogen activators. Journal of Thrombosis and Haemostasis, ‎‎2004;2 (9):1548-1555.‎ https://doi.org/10.1111/j.1538-7836.2004.00884.x
‎18.‎ Sawhney P, Katare K, Sahni G. PEGylation of truncated streptokinase leads to formulation of a ‎useful drug with ameliorated attributes. PLoS One, 2016;11 (5):e0155831.‎ https://doi.org/10.1371/journal.pone.0155831
‎19.‎ Mukhametova L, Aisina R, Tyupa D, Medvedeva A, Gershkovich K. Properties of streptokinase ‎incorporated into polyethylene glycol microcapsules. Russian Journal of Bioorganic Chemistry, ‎‎2013;39 (4):390-396.‎ https://doi.org/10.1134/S1068162013040134
‎20.‎ Leach JK, Edgar A, Patterson E, Miao Y, Johnson AE. Accelerated thrombolysis in a rabbit model of ‎carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase. ‎Thrombosis and haemostasis, 2003;90 (07):64-70.‎ https://doi.org/10.1055/s-0037-1613600
‎21.‎ Baharifar H, Khoobi M, Bidgoli SA, Amani A. Preparation of PEG-grafted chitosan/streptokinase ‎nanoparticles to improve biological half-life and reduce immunogenicity of the enzyme. ‎International journal of biological macromolecules, 2020;143:181-189.‎ https://doi.org/10.1016/j.ijbiomac.2019.11.157
‎22.‎ Aisina R, Mukhametova L, Tyupa D, Gershkovich K, Gulin D, Varfolomeev S. Streptokinase-‎polyethylene glycol conjugates with increased stability and reduced side effects. Russian Journal of ‎Bioorganic Chemistry, 2014;40 (5):516-525.‎ https://doi.org/10.1134/S1068162014050021
‎23.‎ Thummala A, Leach JK, Patterson E, O'Rear E. Effect of encapsulation on plasminogen activator ‎delivery to the microcirculation and its implications for bleeding. Clinical Hemorheology and ‎Microcirculation, 2016;63 (4):373-379.‎ https://doi.org/10.3233/CH-152030
‎24.‎ Koide A, Suzuki S, Kobayashi S. Preparation of polyethylene glycol-modified streptokinase with ‎disappearance of binding ability towards anti-serum and retention of activity. FEBS letters, ‎‎1982;143 (1):73-76.‎ https://doi.org/10.1016/0014-5793(82)80276-7
‎25.‎ Rajagopalan S, Gonias SL, Pizzo SV. A nonantigenic covalent streptokinase-polyethylene glycol ‎complex with plasminogen activator function. The Journal of clinical investigation, 1985;75 ‎‎(2):413-419.‎ https://doi.org/10.1172/JCI111715
‎26.‎ Brucato FH, Pizzo SV. Catabolism of streptokinase and polyethylene glycol-streptokinase: evidence ‎for transport of intact forms through the biliary system in the mouse. Blood, 1990;76 (1):73-79.‎ https://doi.org/10.1182/blood.V76.1.73.bloodjournal76173
‎27.‎ Vauthier C, Bouchemal K. Methods for the preparation and manufacture of polymeric ‎nanoparticles. Pharmaceutical Research, 2009;26:1025-1058.‎ https://doi.org/10.1007/s11095-008-9800-3
‎28.‎ Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. ‎Colloids and surfaces B: biointerfaces, 2010;75 (1):1-18.‎ https://doi.org/10.1016/j.colsurfb.2009.09.001
‎29.‎ Shamsi M, Zahedi P. On-chip preparation of streptokinase entrapped in chitosan nanoparticles ‎used in thrombolytic therapy potentially. Journal of pharmaceutical sciences, 2017;106 (12):3623-‎‎3630.‎ https://doi.org/10.1016/j.xphs.2017.08.001
‎30.‎ Aisina R, Mukhametova L, Gershkovich K, Ivanova E, Zakharyan E, Karakhanov E. Properties of ‎Bioconjugates of Streptokinase with Anionic Polyamidoamine Dendrimers of Various Generations. ‎Russian Journal of Bioorganic Chemistry, 2018;44 (5):528-537.‎ https://doi.org/10.1134/S1068162018040027
31.‎ Abyadeh M, Zarchi AAK, Faramarzi MA, Amani A. Evaluation of factors affecting size and size ‎distribution of chitosan-electrosprayed nanoparticles. Avicenna Journal of Medical Biotechnology, ‎‎2017;9 (3):126.‎
‎32.‎ Yaghoobi N, Majidi RF, ali Faramarzi M, Baharifar H, Amani A. Preparation, optimization and ‎activity evaluation of PLGA/streptokinase nanoparticles using electrospray. Advanced ‎Pharmaceutical Bulletin, 2017;7 (1):131.‎ https://doi.org/10.15171/apb.2017.017
‎33.‎ Modaresi SMS, Ejtemaei Mehr S, Faramarzi MA, Esmaeilzadeh Gharehdaghi E, Azarnia M, ‎Modarressi MH, Baharifar H, Vaez SJ, Amani A. Preparation and characterization of self-assembled ‎chitosan nanoparticles for the sustained delivery of streptokinase: an in vivo study. Pharmaceutical ‎Development and Technology, 2014;19 (5):593-597.‎ https://doi.org/10.3109/10837450.2013.813542
‎34.‎ Baharifar H, Tavoosidana G, Karimi R, Bidgoli SA, Ghanbari H, Faramarzi MA, Amani A. ‎Optimization of self-assembled chitosan/streptokinase nanoparticles and evaluation of their ‎cytotoxicity and thrombolytic activity. Journal of Nanoscience and Nanotechnology, 2015;15 ‎‎(12):10127-10133.‎ https://doi.org/10.1166/jnn.2015.11696
‎35.‎ Hasanpour A, Esmaeili F, Hosseini H, Amani A. Use of mPEG-PLGA nanoparticles to improve ‎bioactivity and hemocompatibility of streptokinase: In-vitro and in-vivo studies. Materials Science ‎and Engineering: C, 2021;118:111427.‎ https://doi.org/10.1016/j.msec.2020.111427
‎36.‎ Baharifar H, Amani A. Cytotoxicity of chitosan/streptokinase nanoparticles as a function of size: an ‎artificial neural networks study. Nanomedicine: Nanotechnology, Biology and Medicine, 2016;12 ‎‎(1):171-180.‎ https://doi.org/10.1016/j.nano.2015.09.002
‎37.‎ Daraee H, Etemadi A, Kouhi M, Alimirzalu S, Akbarzadeh A. Application of liposomes in medicine ‎and drug delivery. Artificial cells, nanomedicine, and biotechnology, 2016;44 (1):381-391.‎ https://doi.org/10.3109/21691401.2014.953633
‎38.‎ Vaidya B, Nayak MK, Dash D, Agrawal GP, Vyas SP. Development and characterization of highly ‎selective target-sensitive liposomes for the delivery of streptokinase: in vitro/in vivo studies. Drug ‎Delivery, 2016;23 (3):791-797.‎ https://doi.org/10.3109/10717544.2014.916770
‎39.‎ Vaidya B, Agrawal G, Vyas SP. Platelets directed liposomes for the delivery of streptokinase: ‎development and characterization. European Journal of Pharmaceutical Sciences, 2011;44 (5):589-‎‎594.‎ https://doi.org/10.1016/j.ejps.2011.10.004
‎40.‎ Vaidya B, Nayak MK, Dash D, Agrawal G, Vyas SP. Development and characterization of site ‎specific target sensitive liposomes for the delivery of thrombolytic agents. International journal of ‎pharmaceutics, 2011;403 (1-2):254-261.‎ https://doi.org/10.1016/j.ijpharm.2010.10.028
‎41.‎ Igor A, Tatyana V, Irina L, Katsiaryna D, Vladimir A. Efficiency of targeted delivery of streptokinase ‎based on fibrin-specific liposomes in the in vivo experiment. Drug Delivery and Translational ‎Research, 2023;13 (3):811-821.‎ https://doi.org/10.1007/s13346-022-01242-2
‎42.‎ Nguyen PD, O'rear E, Johnson AE, Patterson E, Whitsett TL, Bhakta R. Accelerated thrombolysis ‎and reperfusion in a canine model of myocardial infarction by liposomal encapsulation of ‎streptokinase. Circulation research, 1990;66 (3):875-878.‎ https://doi.org/10.1161/01.RES.66.3.875
‎43.‎ Leach K, O Rear E, Miao Y, Johnson A, Patterson E. Thrombolysis in a rabbit stroke model using ‎liposomal-encapsulated streptokinase. Proceedings of the Annual Biochemical ‎Engineering Symposium; 1999:51-55.‎
‎44.‎ Perkins W, Vaughan D, Plavin S, Daley W, Rauch J, Lee L, Janoff A. Streptokinase entrapment in ‎interdigitation-fusion liposomes improves thrombolysis in an experimental rabbit model. ‎Thrombosis and haemostasis, 1997;77 (06):1174-1178.‎ https://doi.org/10.1055/s-0038-1656133
‎45.‎ Nguyen P, O'rear E, Johnson A, Lu R, Fung B. Thrombolysis using liposomal-encapsulated ‎streptokinase: an in vitro study. Proceedings of the Society for Experimental Biology and Medicine, ‎‎1989;192 (3):261-269.‎ https://doi.org/10.3181/00379727-192-42995
‎46.‎ Jin S-E, Kim I-S, Kim C-K. Comparative effects of PEG-containing liposomal formulations on in vivo ‎pharmacokinetics of streptokinase. Archives of Pharmacal Research, 2015;38 (10):1822-1829.‎ https://doi.org/10.1007/s12272-015-0594-7
‎47.‎ Adzerikho I, Vladimirskaya T, Lutsik I, Dubatouka K, Agabekov V, Branovitskaya E, Chernyavsky E, ‎Lugovska N. Fibrinspecific liposomes as a potential method of delivery of the thrombolytic ‎preparation streptokinase. Journal of Thrombosis and Thrombolysis, 2022;53 (2):313-320.‎ https://doi.org/10.1007/s11239-021-02614-0
‎48.‎ Erdoğan S, Oezer AY, Volkan B, Caner B, Bilgili H. Thrombus localization by using streptokinase ‎containing vesicular systems. Drug Delivery, 2006;13 (4):303-309.‎ https://doi.org/10.1080/10717540600559544
‎49.‎ Holt B, Gupta AS. Streptokinase loading in liposomes for vascular targeted nanomedicine ‎applications: encapsulation efficiency and effects of processing. Journal of Biomaterials ‎applications, 2012;26 (5):509-527.‎ https://doi.org/10.1177/0885328210374778
‎50.‎ Wang X, Inapagolla R, Kannan S, Lieh-Lai M, Kannan RM. Synthesis, characterization, and in vitro ‎activity of dendrimer− Streptokinase conjugates. Bioconjugate chemistry, 2007;18 (3):791-799.‎ https://doi.org/10.1021/bc060322d
‎51.‎ Nguyen HX, O'Rear EA. An in vitro thrombolysis study using a mixture of fast-acting and slower ‎release microspheres. Pharmaceutical research, 2016;33 (7):1552-1563.‎ https://doi.org/10.1007/s11095-016-1897-1
‎52.‎ Rassam H, Allameh A, Eidi A, Alebouyeh M, Doroud D. Streptokinase Loaded Solid Lipid ‎Nanoparticles: Preparation and Charactrization. Archives of Pharmacy Practice, 2019;1:178.‎
‎53.‎ Rassam H, Allameh A, Eidi A, Alebouyeh M, Doroud D. Novel Formulation for Recombinant ‎Streptokinase by Solid Lipid Nanoparticle: A Light at the End of the Tunnel. Archives of Pharmacy ‎Practice, 2020;1:149.‎