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  • Title: Hyaluronated nanoparticles with pH- and enzyme-responsive drug release properties.
    Author: Kim SW, Oh KT, Youn YS, Lee ES.
    Journal: Colloids Surf B Biointerfaces; 2014 Apr 01; 116():359-64. PubMed ID: 24521699.
    Abstract:
    In this study, we report the development of a novel pH-responsive nanoparticle composed of hyaluronic acid (HA) grafted with functional 3-diethylaminopropyl (DEAP) groups (HA-g-DEAP). The pH-responsive nanoparticles were fabricated by a self-assembled arrangement of a hydrophilic block (HA) and a hydrophobic block (non-protonated DEAP) of HA-g-DEAP at pH 7.4. HA-g-DEAP was prepared by a simple conjugation of the carboxylic acid groups of HA and the free amine groups of DEAP. The HA-g-DEAP nanoparticles displayed pH-dependent changes in their physicochemical properties. We observed nanoparticle destabilization because of the protonation of DEAP when the pH of the solution decreased to 5.0. This phenomenon resulted in the release of the encapsulated content (model drug, doxorubicin: DOX) from the nanoparticle core. In addition, the degradation of HA by hyaluronidase (Hyal) significantly accelerated the DOX release rate, which may allow for increased drug release in diseased cells with acidic endosomal pH (∼pH 5.0) in the presence of Hyal. Overall, a significant improvement in the drug release rate was evident when this nanoparticle system was stimulated by both an acidic pH and specific enzymes.
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