Yang Chen,Jie Zhang,Wenhao Xiao,Anfu Chen,Zhixian Dong,Jinbao Xu,Wenhua Xu,Caihong Lei
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) was used as organocatalyst to reinvestigate the ring-opening polymerization (ROP) of ε -caprolactone (CL) with benzyl alcohol (BnOH) initiator in bulk at 90 °C considering the unsuccessful ROP of CL at RT in previously reported publications. Kinetic study indicates that the PCLs could be well-designed with a controlled/living character of polymerization. The use of functional initiators, such as 2-hydroxyethyl methacrylate (HEMA), propargyl alcohol (PGA), 6-azido-1-hexanol (AHA) and methoxy poly(ethylene glycol) (mPEG) leads to end-functionalized PCLs. Accordingly, the block copolymerization of CL with δ-valerolactone (VL), trimethylene carbonate (TMC) and lactide (LA) successfully proceeded to give PCL- b -PVL, PCL- b -PTMC and PCL- b -PLA copolymers. Finally, the reaction mechanism was studied with DFT calculations and NMR measurements.
Xiao Duan,Qiang Wang,Yue Wang,Xinping Liu,Manman Lu,Zhifang Li,Xuelian Jiang,Jingquan Ji
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.
危险品化学品经营许可证（带存储）