Glutathione-responsive self-delivery nanoparticles assembled by curcumin dimer for enhanced intracellular drug delivery

Publication date: Available online 31 July 2018Source: International Journal of PharmaceuticsAuthor(s): Huabing Zhang, Yubin Zhang, Yilin Chen, Ying Zhang, Yange Wang, Yinying Zhang, Liang Song, Beili Jiang, Guanghao Su, Yang Li, Zhenqing HouAbstractPoor water solubility, short half-life, and low drug efficacy posed a challenge for clinical application of curcumin (CUR). In this work, a kind of CUR prodrug was synthesized by coupling two CUR molecules with a mono-thioether linker for glutathione (GSH)-responsive drug delivery. The synthesized CUR prodrug (CUR-S-CUR dimer) could self-assemble into the homogeneous spherical nanoparticles (NPs) in aqueous solution followed by surface functionalization of trace amounts of DSPE-PEG. These CUR-S-CUR@PEG NPs exhibited a small particle size of ∼100 nm, high CUR-loading content of ∼78 wt%, and good colloid stability. Moreover, the CUR-S-CUR@PEG NPs demonstrated much more efficient cellular uptake and intracellular/nuclear drug delivery compared with free CUR, indicating the advantages of small molecular prodrug assembly. In addition, the GSH with high concentration in tumor cells could trigger the disassembly of CUR-S-CUR@PEG NPs. Furthermore, the cytotoxicity assays indicated that the CUR-S-CUR@PEG NPs exhibited the comparable inhibition effect of tumor cell proliferation with free CUR due to sustained drug release. Therefore, these stimuli-responsive CUR-S-CUR@PEG NPs might have promising potential for highly efficient intracell...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research