Preparation of Glutathione-Responsive Paclitaxel Prodrug Based on Endogenous Molecule of L-Glutathione Oxidized for Cancer Therapy
Xiao Duan,
Qiang Wang,
Yue Wang,
Xinping Liu,
Manman Lu,
Zhifang Li,
Xuelian Jiang,
Jingquan Ji
Affiliations
Xiao Duan
Changzhi Key Laboratory of Drug Molecular Design and Innovative Pharmaceutics, Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, China
Qiang Wang
Changzhi Key Laboratory of Drug Molecular Design and Innovative Pharmaceutics, Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, China
Yue Wang
Central Lab Changzhi Medical College, Changzhi Medical College, Changzhi 046000, China
Xinping Liu
Changzhi Key Laboratory of Drug Molecular Design and Innovative Pharmaceutics, Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, China
Manman Lu
Central Lab Changzhi Medical College, Changzhi Medical College, Changzhi 046000, China
Zhifang Li
Changzhi Key Laboratory of Drug Molecular Design and Innovative Pharmaceutics, Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, China
Xuelian Jiang
Changzhi Key Laboratory of Drug Molecular Design and Innovative Pharmaceutics, Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, China
Jingquan Ji
Central Lab Changzhi Medical College, Changzhi Medical College, Changzhi 046000, China
Using an endogenous carrier is the best method to address the biocompatibility of carriers in the drug delivery field. Herein, we prepared a glutathione-responsive paclitaxel prodrug micelle based on an endogenous molecule of L-glutathione oxidized (GSSG) for cancer therapy using one-pot synthesis. The carboxyl groups in L-glutathione oxidized were reacted with the hydroxyl group in paclitaxel (PTX) using the catalysts dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). Then, the amino-polyethylene glycol monomethyl ether (mPEG-NH2) was conjugated with GSSG to prepare PTX-GSSG-PEG. The structure of PTX-GSSG-PEG was characterized using infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS). The drug release kinetics of PTX within PTX-GSSG-PEG were quantified using ultraviolet spectroscopy (UV-Vis). The size of the PTX-GSSG-PEG micelles was 83 nm, as evaluated using dynamic light scattering (DLS), and their particle size remained stable in a pH 7.4 PBS for 7 days. Moreover, the micelles could responsively degrade and release PTX in a reduced glutathione environment. The drug loading of PTX in PTX-GSSG-PEG was 13%, as determined using NMR. Furthermore, the cumulative drug release rate of PTX from the micelles reached 72.1% in a reduced glutathione environment of 5 mg/mL at 120 h. Cell viability experiments demonstrated that the PTX-GSSG-PEG micelles could induce the apoptosis of MCF-7 cells. Additionally, cell uptake showed that the micelles could distribute to the cell nuclei within 7 h. To sum up, with this glutathione-responsive paclitaxel prodrug micelle based on the endogenous molecule GSSG, it may be possible to develop novel nanomedicines in the future.
