Streptokinase entrapment in interdigitation-fusion liposomes improves thrombolysis in an experimental rabbit model
The successful design of new thrombolytic agents depends on providing these agents with increased clot selectivity. As recently demonstrated (10), entrapment of tissue plasminogen activator into liposomes apparently provided the selective targeting needed to improve the efficacy of this fibrinolytic agent. To test whether liposomal entrapment would benefit streptokinase, a fibrinolytic agent with a different mode of action and inactivation, we compared liposomal streptokinase with free streptokinase in an experimental rabbit model of thrombolysis. First we adapted a new method to produce liposomes of high entrapment efficiency, termed interdigitation-fusion (IF) liposomes, for the encapsulation of streptokinase. This system was then tested in an in vivo rabbit model of thrombolysis where animals with established clots were infused with either free streptokinase (40,000 U/kg), liposomally entrapped streptokinase, free streptokinase+empty liposomes, or the corresponding amount of empty liposomes or saline. Significant differences (p < 0.05) in the percent clot lysis were observed between saline control (22.4 +/- 3.3%; mean +/- S.E.), free streptokinase (36.3 +/- 3.4%), and liposomal streptokinase (47.4 +/- 1.4%). Importantly, animals treated with empty liposomes experienced a level of thrombolysis (32.4 +/- 2.8%) not different to that produced by free streptokinase or empty liposomes plus free streptokinase (38.0 +/- 2.0%). We believe the effect of liposomes alone is due to a transient redistribution or margination of circulating platelets. When tested in rabbits immunized against streptokinase, liposomal (33.8 +/- 1.5%) but not free streptokinase (29.3 +/- 2.1%) showed significant thrombolytic activity compared to saline (22.4 +/- 3.3%) (p < 0.05). The thrombolytic activity was comparable to free streptokinase in non-immunized rabbits. This suggests liposomal streptokinase would have better thrombolytic activity than streptokinase alone and still provide to those patients possessing high levels of anti-streptokinase antibodies (5% of the population) the equivalent degree of therapy expected from free streptokinase.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1997 |
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| Erschienen: |
1997 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:77 |
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| Enthalten in: |
Thrombosis and haemostasis - 77(1997), 6 vom: 30. Juni, Seite 1174-8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Perkins, W R [VerfasserIn] |
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| Themen: |
Drug Carriers |
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| Anmerkungen: |
Date Completed 11.09.1997 Date Revised 15.11.2006 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM091959292 |
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| 100 | 1 | |a Perkins, W R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Streptokinase entrapment in interdigitation-fusion liposomes improves thrombolysis in an experimental rabbit model |
| 264 | 1 | |c 1997 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Completed 11.09.1997 | ||
| 500 | |a Date Revised 15.11.2006 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The successful design of new thrombolytic agents depends on providing these agents with increased clot selectivity. As recently demonstrated (10), entrapment of tissue plasminogen activator into liposomes apparently provided the selective targeting needed to improve the efficacy of this fibrinolytic agent. To test whether liposomal entrapment would benefit streptokinase, a fibrinolytic agent with a different mode of action and inactivation, we compared liposomal streptokinase with free streptokinase in an experimental rabbit model of thrombolysis. First we adapted a new method to produce liposomes of high entrapment efficiency, termed interdigitation-fusion (IF) liposomes, for the encapsulation of streptokinase. This system was then tested in an in vivo rabbit model of thrombolysis where animals with established clots were infused with either free streptokinase (40,000 U/kg), liposomally entrapped streptokinase, free streptokinase+empty liposomes, or the corresponding amount of empty liposomes or saline. Significant differences (p < 0.05) in the percent clot lysis were observed between saline control (22.4 +/- 3.3%; mean +/- S.E.), free streptokinase (36.3 +/- 3.4%), and liposomal streptokinase (47.4 +/- 1.4%). Importantly, animals treated with empty liposomes experienced a level of thrombolysis (32.4 +/- 2.8%) not different to that produced by free streptokinase or empty liposomes plus free streptokinase (38.0 +/- 2.0%). We believe the effect of liposomes alone is due to a transient redistribution or margination of circulating platelets. When tested in rabbits immunized against streptokinase, liposomal (33.8 +/- 1.5%) but not free streptokinase (29.3 +/- 2.1%) showed significant thrombolytic activity compared to saline (22.4 +/- 3.3%) (p < 0.05). The thrombolytic activity was comparable to free streptokinase in non-immunized rabbits. This suggests liposomal streptokinase would have better thrombolytic activity than streptokinase alone and still provide to those patients possessing high levels of anti-streptokinase antibodies (5% of the population) the equivalent degree of therapy expected from free streptokinase | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Drug Carriers |2 NLM | |
| 650 | 7 | |a Fibrinolytic Agents |2 NLM | |
| 650 | 7 | |a Liposomes |2 NLM | |
| 650 | 7 | |a Streptokinase |2 NLM | |
| 650 | 7 | |a EC 3.4.- |2 NLM | |
| 700 | 1 | |a Vaughan, D E |e verfasserin |4 aut | |
| 700 | 1 | |a Plavin, S R |e verfasserin |4 aut | |
| 700 | 1 | |a Daley, W L |e verfasserin |4 aut | |
| 700 | 1 | |a Rauch, J |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, L |e verfasserin |4 aut | |
| 700 | 1 | |a Janoff, A S |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Thrombosis and haemostasis |d 1979 |g 77(1997), 6 vom: 30. Juni, Seite 1174-8 |w (DE-627)NLM000103896 |x 2567-689X |7 nnns |
| 773 | 1 | 8 | |g volume:77 |g year:1997 |g number:6 |g day:30 |g month:06 |g pages:1174-8 |
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| 952 | |d 77 |j 1997 |e 6 |b 30 |c 06 |h 1174-8 | ||