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  • Title: Folate modified dual pH/reduction-responsive mixed micelles assembled using FA-PEG-PDEAEMA and PEG-SS-PCL for doxorubicin delivery.
    Author: Yang C, Wang D, Liu W, Yang Z, He T, Chen F, Lin W.
    Journal: Phys Chem Chem Phys; 2023 May 03; 25(17):12458-12468. PubMed ID: 37096448.
    Abstract:
    Aiming at achieving the concurrent performances of high loading, well controlled release and active targeted delivery, folate (FA) modified dual pH/reduction-responsive mixed polymeric micelles were rationally assembled using FA-PEG-PDEAEMA and PEG-SS-PCL by dissipative particle dynamics (DPD) simulations. The optimized polymers PEG112-PDEAEMA40, FA-PEG112-PDEAEMA40, and PEG112-SS-PCL70 were synthesized and characterized using 1H NMR, FT-IR and GPC, and their mixed micelles were applied for doxorubicin (DOX) delivery. The drug loading capacity (LC) and encapsulation efficiency (EE) values of the MIX1 (FA-PEG112-PDEAEMA40/PEG112-SS-PCL70) at a DOX/polymer feeding ratio of 15 mg/30 mg were 20.22% and 50.69%, which were higher than those of single polymer micelles and MIX2 (PEG112-PDEAEMA40/PEG112-SS-PCL70). Particle size distributions, mesoscopic morphologies, DPD simulations and in vitro drug release profiles all confirmed the well-controlled release performance of the DOX-loaded micelles formed by MIX1: slow DOX release with a cumulative release of 20.46% in the neutral environment and accelerated release with a cumulative release of 74.20% at pH 5.0 + 10 mM DTT within 120 h, which were similar to those of MIX2. Cytotoxicity assay found that both MIX1 and MIX2 blank micelles were biocompatible, and a superior inhibitory effect of the FA-modified DOX-loaded micelles MIX1 on HepG2 cells was found compared to that of free DOX and non-FA-modified DOX-loaded micelles MIX2. All of these confirmed the superiority of MIX1 micelles with high loading capacity, well controlled release, and enhanced inhibitory effects on HepG2 cells, which might be a prospective candidate for anticancer drug delivery.
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