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The synthesis and co-micellization of PCL-P(HEMA/HEMA-LA) and PCL-P(HEMA/HEMA-FA) as shell cross-linked drug carriers with target/redox properties.
Journal of Biomaterials Science. Polymer Edition 2018 December 18
In order to obtain target/redox shell cross-linked micelles (TCM), copolymers poly(ε-caprolactone)-poly(2-hydroxyethyl methacrylate/methacrylate-alpha lipoic acid) and poly(ε-caprolactone)-poly(2-hydroxyethyl methacrylate/methacrylate-folate, PCL-P(HEMA/HEMA-LA) and PCL-P(HEMA/HEMA-FA) were designed and synthesized. The copolymers PCL-P(HEMA/HEMA-LA) could form reduction-sensitive cross-linked micelles (CM) by using a catalytic amount of DTT. The micelles maintained high stability against dilution but were destroyed in 10 mM dithiothreitol (DTT). The drug loaded content (DLC) of CM was 8.9%, which was almost twice as much as non-cross-linked micelle (NCM). In vitro drug release at pH 7.4 showed that the cumulative release rate of CM in 36 h was less than 30%, while it was about 50% for NCM. When PCL-P(HEMA/HEMA-LA) and PCL-P(HEMA/HEMA-FA) (FA 1%, 3% and 5%) formed target/redox micelles, IC50 of TCM with FA 3% was the lowest (1.4 μg/mL) to Hela cells with excessive expression folate receptors. The cell uptake of TCM by Hela cells is higher than target non-cross-linked micelles (TNCM), while there was not much difference between both micelles uptaken by A549 cells, which are lack of folate receptors. Therefore, the drug carriers of TCM have potential to be explored as shell cross-linked target/redox drug carriers to the cancer cells on the surface with excessive folate receptors.
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