Investigation of chitosan‐g‐PEG grafted nanoparticles as a half‐life enhancer carrier for tissue plasminogen activator delivery |
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Authors: | Arezoo Khosravi Hadi Baharifar Mohamad Hasan Darvishi Ali Akbar Karimi Zarchi |
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Affiliation: | 1. Atherosclerosis Research Center, Baqiyatallah University of Medical Science, Tehran Iran ; 2. Department of Medical Nanotechnology, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran Iran ; 3. Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran Iran |
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Abstract: | Tissue plasminogen activator (tPA) a thrombolytic agent is commonly used for digesting the blood clot. tPA half‐life is low (4–6 min) and its administration needs a prolonged continuous infusion. Improving tPA half‐life could reduce enzyme dosage and enhance patient compliance. Nano‐carries could be used as delivery systems for the protection of enzymes physically, enhancing half‐life and increasing the stability of them. In this study, chitosan (CS) and polyethylene glycol (PEG) were used for the preparation of CS‐g‐PEG/tPA nanoparticles (NPs) via the ion gelation method. Particles’ size and loading capacity were optimised by central composite design. Then, NPs cytotoxicity, release profile, enzyme activity and in vivo half‐life and coagulation time were investigated. The results showed that NPs does not have significant cytotoxicity. Release study revealed that a burst effect happened in the first 5 min and resulted in releasing 30% of tPA. Loading tPA in NPs could decrease 25% of its activity but the half‐life of it increases in comparison to free tPA in vivo. Also, blood coagulation time has significantly affected (p ‐value = 0.041) by encapsulated tPA in comparison to free tPA. So, CS‐g‐PEG/tPA could increase enzyme half‐life during the time and could be used as a non‐toxic candidate delivery system for tPA.Inspec keywords: drug delivery systems, nanofabrication, drugs, nanomedicine, coagulation, biomedical materials, cellular biophysics, enzymes, biochemistry, toxicology, molecular biophysics, biological tissues, blood, nanoparticles, polymersOther keywords: chitosan‐g‐PEG grafted nanoparticles, half‐life enhancer carrier, tissue plasminogen activator delivery, tPA half‐life, prolonged continuous infusion, enzyme dosage, polyethylene glycol, cytotoxicity, enzyme activity, encapsulated tPA, enzyme half‐life, blood coagulation, time 5.0 min |
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