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Liposomal nanocarriers for plasminogen activators
S. Koudelka, R. Mikulik, J. Mašek, M. Raška, P. Turánek Knotigová, AD. Miller, J. Turánek,
Language English Country Netherlands
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
- MeSH
- Urokinase-Type Plasminogen Activator administration & dosage therapeutic use MeSH
- Fibrinolytic Agents administration & dosage therapeutic use MeSH
- Humans MeSH
- Liposomes chemistry ultrastructure MeSH
- Metalloendopeptidases administration & dosage therapeutic use MeSH
- Nanostructures chemistry ultrastructure MeSH
- Fibrinolysin administration & dosage therapeutic use MeSH
- Streptokinase administration & dosage therapeutic use MeSH
- Tissue Plasminogen Activator administration & dosage therapeutic use MeSH
- Thromboembolism drug therapy MeSH
- Thrombolytic Therapy methods MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Several plasminogen activators (PAs) have been found effective in treating different thromboembolic diseases. However, administration of conventional thrombolytic therapy is limited by a low efficacy of present formulations of PAs. Conventional treatments using these therapeutic proteins are associated with several limitations including rapid inactivation and clearance, short half-life, bleeding complications or non-specific tissue targeting. Liposome-based formulations of PAs such as streptokinase, tissue-plasminogen activator and urokinase have been developed to improve the therapeutic efficacy of these proteins. Resulting liposomal formulations were found to preserve the original activity of PAs, promote their selective delivery and improve thrombus targeting. Therapeutic potential of these liposome-based PAs has been demonstrated successfully in various pre-clinical models in vivo. Reductions in unwanted side effects (e.g., hemorrhage or immunogenicity) as well as enhancements of efficacy and safety were achieved in comparison to currently existing treatment options based on conventional formulations of PAs. This review summarizes present achievements in: (i) preparation of liposome-based formulations of various PAs, (ii) development of PEGylated and targeted liposomal PAs, (iii) physico-chemical characterization of these developed systems, and (iv) testing of their thrombolytic efficacy. We also look to the future and the imminent arrival of theranostic liposomal formulations to move this field forward.
Department of Immunology Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic
Department of Pharmacology and Immunotherapy Veterinary Research Institute Brno Czech Republic
International Clinical Research Center St Anne's University Hospital Brno Czech Republic
Neurology Department of Masaryk University and St Anne's University Hospital Brno Czech Republic
References provided by Crossref.org
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- $a Several plasminogen activators (PAs) have been found effective in treating different thromboembolic diseases. However, administration of conventional thrombolytic therapy is limited by a low efficacy of present formulations of PAs. Conventional treatments using these therapeutic proteins are associated with several limitations including rapid inactivation and clearance, short half-life, bleeding complications or non-specific tissue targeting. Liposome-based formulations of PAs such as streptokinase, tissue-plasminogen activator and urokinase have been developed to improve the therapeutic efficacy of these proteins. Resulting liposomal formulations were found to preserve the original activity of PAs, promote their selective delivery and improve thrombus targeting. Therapeutic potential of these liposome-based PAs has been demonstrated successfully in various pre-clinical models in vivo. Reductions in unwanted side effects (e.g., hemorrhage or immunogenicity) as well as enhancements of efficacy and safety were achieved in comparison to currently existing treatment options based on conventional formulations of PAs. This review summarizes present achievements in: (i) preparation of liposome-based formulations of various PAs, (ii) development of PEGylated and targeted liposomal PAs, (iii) physico-chemical characterization of these developed systems, and (iv) testing of their thrombolytic efficacy. We also look to the future and the imminent arrival of theranostic liposomal formulations to move this field forward.
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