Open AccessInvestigation of chitosan‐g‐PEG grafted nanoparticles as a half‐life enhancer carrier for tissue plasminogen activator delivery
Author(s) -
Khosravi Arezoo,
Baharifar Hadi,
Darvishi Mohamad Hasan,
Karimi Zarchi Ali Akbar
Publication year - 2020
Publication title -
iet nanobiotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.366
H-Index - 38
eISSN - 1751-875X
pISSN - 1751-8741
DOI - 10.1049/iet-nbt.2019.0304
Subject(s) - tissue plasminogen activator , peg ratio , polyethylene glycol , in vivo , chemistry , plasminogen activator , chitosan , t plasminogen activator , cytotoxicity , pharmacology , materials science , biochemistry , in vitro , medicine , microbiology and biotechnology , finance , economics , biology
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.