PREPARATION OF COMPLEX FORMULATIONS BASED ON LIPOSOMAL STREPTOKINASE AND THEIR PHARMACOKINETIC CHARACTERISTICS
Abstract
It was obtained that liposomal streptokinase (SK) with a hydrodynamic diameter of ~70 nm and a zeta-potential of –6.2 mV contains 14.1 % wt of drug. The complex formulations based on liposomal SK include “associated” and “free” SK in the ratios of 20/80, 40/60 and 50/50. The in vivo experiments on rats showed an increase in the elimination half-time from 1.8 to 31.9 min and in the time to reach the maximum concentration of streptokinase from 15 to 45 min. The decrease in the elimination rate constant by a factor of 18 compared with SK was also found. The optimal ratio of “associated” and “free” SK in the complex formulation was 40 and 60 % respectively. It was used to obtain liposomal fibrin-specific form of thrombolytic with similar physico-chemical and pharmacokinetic parameters.
About the Authors
Katsiaryna I. Dubatouka
Institute of Chemistry of New Materials of the National Academy of Sciences of Belarus, Minsk
Belarus
Belarus
Junior researcher
36, F. Skoryna Str., 220141
Iryna L. Lutsik
Belarussian Medical Academy of Postgraduate Education, Minsk
Belarus
Belarus
Junior researcher
3/3, P. Brovka Str., 220013
Evgenii A. Cherniavsky
Research Institute for Physical Chemical Problems of the Belarusian State University, Minsk
Belarus
Belarus
Ph. D. (Chemistry), Deputy Director
14, Leningradskaya Str., 220030
Ekaterina S. Bondarenko
Research Institute for Physical Chemical Problems of the Belarusian State University, Minsk
Belarus
Belarus
Junior researcher
14, Leningradskaya Str., 220030
Igor E. Adzerikho
Belarussian Medical Academy of Postgraduate Education, Minsk
Belarus
Belarus
D. Sc. (Medicine), Professor
3/3, P. Brovka Str., 220013
Vladimir E. Agabekov
Institute of Chemistry of New Materials of the National Academy of Sciences of Belarus, Minsk
Belarus
Belarus
Academician, D. Sc. (Chemistry), Professor, Director
36, F. Skoryna Str., 220141
References
1. Kesov P. G., Reytblat O. M., Safiullina Z. M., Shalaev S. V. Evolution of thrombolytic therapy in the treatment of myocardial infarction. Ratsional’naya farmakoterapiya v kardiologii = Rational Pharmacotherapy in Cardiology, 2014, vol. 10, no. 5, pp. 554–558 (in Russian).
2. Sharafutdinova A. F., Menzorov M. V. Complications of thrombolytic therapy in actual clinical practice. Klinitsist = The Clinician, 2011, no. 3, pp. 106–108 (in Russian). doi.org/10.17650/1818-8338-2011-3-106-108
3. Bunker A., Magarkar A., Viitala T. Rational design of liposomal drug delivery systems, a review: Combined experimental and computational studies of lipid membranes, liposomes and their PEGylation. Biochimica et Biophysica Acta (BBA) – Biomembranes, 2016, vol. 1858, no. 10, pp. 2334–2352. doi.org/10.1016/j.bbamem.2016.02.025
4. Dubatouka K. I., Agabekov V. Е., Lutsik I. L., Yatsevich V. N., Adzerikho I. E. Effect of liposomal streptokinase on the D-dimers formation. Doklady Natsional’noi akademii nauk Belarusi = Doklady of the National Academy of Sciences of Belarus, 2016, vol. 60, no. 6, pp. 54–58 (in Russian).
5. Dubatouka K. I., Paribok I. V., Agabekov V. E. Investigation of antibody modified liposomes binding with patterned fibrinogen films. Physics, chemistry and application of nanostructures. Singapore, World Scientific, 2017, pp. 299–302. doi. org/10.1142/9789813224537_0069
6. Lutik I. L., Dubatovka K. I., Adzeriho I. E. Comparative evaluation of pharmacokinetics liposomal forms of streptokinase in experiment in vivo. Vestnik Rossiiskogo gosudarstvennogo meditsinskogo universiteta = Bulletin of Russian State Medical University, 2015, no. 2, pp. 864–865 (in Russian).
7. Walde P., Ichikawa S. Enzymes inside lipid vesicles: preparation, reactivity and applications. Biomolecular Engineering, 2001, vol. 18, no. 4, pp. 143–177. doi.org/10.1016/s1389-0344(01)00088-0
8. Kukes V. G. (ed.). Clinical pharmacology. 3d ed. Moscow, GEOTAR–Media Publ., 2006, pp. 17–69 (in Russian).
9. Markowitz J. S., Straughn A. B., Patrick K. S., DeVane C. L., Pestreich L., Lee J., Wang Y., Muniz R. Pharmacokinetics of Methylphenidate after oral administration of two modified-release formulations in helthy adults. Clinical Pharmacokinetics, 2003, vol. 42, no. 4, pp. 393–401. doi.org/10.2165/00003088-200342040-00007
10. Gabrielsson J., Weiner D. Pharmacokinetic and Pharmacodynamic Data Analysis – Concepts and Applications. 5th ed. Swedish Pharmaceutical Press, 2016. 1040 p.
11. Thompson A. K., Mozafari M. R., Singh H. The properties of liposomes produced from milk fat globule membrane material using different techniques. Le Lait, 2007, vol. 87, no. 4–5, pp. 349–360. doi.org/10.1051/lait:2007013
12. Vaidya B., Nayak M. K., Dash D., Agrawal G. P., Vyas S. P. Development and characterization of site specific target sensitive liposomes for the delivery of thrombolytic agents. International Journal of Pharmaceutics, 2011, vol. 403, no. 1–2, pp. 254–261. doi.org/10.1016/j.ijpharm.2010.10.028
13. Absar S., Nahar K., Kwon Y. M., Ahsan F. Thrombus-targeted nanocarrier attenuates bleeding complications associated with conventional thrombolytic therapy. Pharmaceutical Research, 2013, vol. 30, no. 6, pp. 1663–1676. doi.org/10.1007/ s11095-013-1011-x
14. Holt B., Sen Gupta A. Streptokinase Loading in Liposomes for Vascular Targeted Nanomedicine Applications: Encapsulation Efficiency and Effects of Processing. Journal of Biomaterials Applications, 2010, vol. 26, no. 5, pp. 509–527. doi. org/10.1177/0885328210374778
Review
Views: 643
Email this article 