Efficiency of targeted delivery of streptokinase based on fibrin-specific liposomes in the in vivo experiment
Acute thrombosis has a narrow therapeutic window and remains the leading cause of morbidity and mortality, while thrombolytic therapy has limited efficacy and risk of side effects. We have developed and investigated new fibrin-specific systems for local drug delivery to increase efficiency while minimizing the side effects of streptokinase. The experiment was carried out on dogs with 2-h thrombi in the femoral artery received intravenous injections of streptokinase, liposome-bound and free streptokinase at 40/60% ratio, and immunoliposomes. The completeness of the vessel lumen restoration affected by the thrombus, and the risks of side effects were assessed. Fibrinolytic parameters (plasminogen, fibrinogen, alpha2-antiplasmin, and D-dimers levels) were measured at several time points after thrombus induction and the administration of the drug. There was a strong activation of fibrinolysis and consumption of fibrinolysis inhibitors after therapy with all liposomal forms of streptokinase. According to the ultrasound data, immunoliposomal form of streptokinase significantly reduces the degree of residual stenosis to 32% [30.5; 33.7] in 180 min after injection. The high fibrinolytic effect of liposomal forms of streptokinase is not accompanied by a sharp drop in the fibrinogen concentration in the blood compared to the native streptokinase by 60 min. The morphometric evaluation of the artery samples showed that immunoliposomal form of streptokinase induces a significant increase in the degree of free vascular lumen compared to the native streptokinase (71.3% (62.7; 77.5) vs. 47.7% (39.6; 55.7), p < 0.001). Thus, the study shows the efficacy of streptokinase-induced thrombolysis using immunoliposomal form of drug delivery system. Graphical abstract Mechanism of action of the immunoliposomal delivery system.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
Drug Delivery and Translational Research - 13(2022), 3 vom: 04. Okt., Seite 811-821 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Igor, Adzerikho [VerfasserIn] |
|---|
| Links: |
Volltext [lizenzpflichtig] |
|---|
| Themen: |
Fibrin-specific monoclonal antibodies |
|---|
| Anmerkungen: |
© Controlled Release Society 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
|---|
| doi: |
10.1007/s13346-022-01242-2 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
SPR049214063 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | SPR049214063 | ||
| 003 | DE-627 | ||
| 005 | 20230519105204.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230202s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s13346-022-01242-2 |2 doi | |
| 035 | |a (DE-627)SPR049214063 | ||
| 035 | |a (SPR)s13346-022-01242-2-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Igor, Adzerikho |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Efficiency of targeted delivery of streptokinase based on fibrin-specific liposomes in the in vivo experiment |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © Controlled Release Society 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. | ||
| 520 | |a Acute thrombosis has a narrow therapeutic window and remains the leading cause of morbidity and mortality, while thrombolytic therapy has limited efficacy and risk of side effects. We have developed and investigated new fibrin-specific systems for local drug delivery to increase efficiency while minimizing the side effects of streptokinase. The experiment was carried out on dogs with 2-h thrombi in the femoral artery received intravenous injections of streptokinase, liposome-bound and free streptokinase at 40/60% ratio, and immunoliposomes. The completeness of the vessel lumen restoration affected by the thrombus, and the risks of side effects were assessed. Fibrinolytic parameters (plasminogen, fibrinogen, alpha2-antiplasmin, and D-dimers levels) were measured at several time points after thrombus induction and the administration of the drug. There was a strong activation of fibrinolysis and consumption of fibrinolysis inhibitors after therapy with all liposomal forms of streptokinase. According to the ultrasound data, immunoliposomal form of streptokinase significantly reduces the degree of residual stenosis to 32% [30.5; 33.7] in 180 min after injection. The high fibrinolytic effect of liposomal forms of streptokinase is not accompanied by a sharp drop in the fibrinogen concentration in the blood compared to the native streptokinase by 60 min. The morphometric evaluation of the artery samples showed that immunoliposomal form of streptokinase induces a significant increase in the degree of free vascular lumen compared to the native streptokinase (71.3% (62.7; 77.5) vs. 47.7% (39.6; 55.7), p < 0.001). Thus, the study shows the efficacy of streptokinase-induced thrombolysis using immunoliposomal form of drug delivery system. Graphical abstract Mechanism of action of the immunoliposomal delivery system | ||
| 650 | 4 | |a Streptokinase |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Local delivery system |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Liposome |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Immunoliposome |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Fibrinolysis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Fibrin-specific monoclonal antibodies |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Tatyana, Vladimirskaya |4 aut | |
| 700 | 1 | |a Irina, Lutsik |4 aut | |
| 700 | 1 | |a Katsiaryna, Dubatouka |0 (orcid)0000-0003-0089-5396 |4 aut | |
| 700 | 1 | |a Vladimir, Agabekov |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Drug Delivery and Translational Research |d New York, NY [u.a.] : Springer, 2011 |g 13(2022), 3 vom: 04. Okt., Seite 811-821 |w (DE-627)SPR031406076 |w (DE-600)2590155-2 |x 2190-3948 |7 nnns |
| 773 | 1 | 8 | |g volume:13 |g year:2022 |g number:3 |g day:04 |g month:10 |g pages:811-821 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1007/s13346-022-01242-2 |z lizenzpflichtig |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_SPRINGER | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |d 13 |j 2022 |e 3 |b 04 |c 10 |h 811-821 | ||