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Liposomal nanocarriers for plasminogen activators

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KOUDELKA Stepan MIKULÍK Robert MAŠEK Josef RAŠKA Milan KNOTIGOVÁ Pavlína Turánek MILLER Andrew D. TURÁNEK Jaroslav

Rok publikování 2016
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Controlled Release
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Doi http://dx.doi.org/10.1016/j.jconrel.2016.02.019
Obor Kardiovaskulární nemoci včetně kardiochirurgie
Klíčová slova Fibrin; Liposomes; Platelets; Protein delivery; RGD peptide; Streptokinase; Stroke; Thrombus; Tissue plasminogen activator; Urokinase
Popis 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) physicochemical 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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