Construction and Characterization of Docetaxel pH-Sensitive Micelles Modified by Poly(2-ethyl-2-oxazoline)-Cholesterol Methyl Carbonate
ZHANG Tian-yu1,2, WANG Kai-qian3, ZHANG Jing1*, SU Hong2, XU Huan1,2*
1. Jiangxi University of Chinese Medicine, Nanchang 330004, China; 2. College of Chemistry and Chemical Engineering,Liaoning Normal University,Dalian 116029, China; 3. Northeast Pharmaceutical Group Co., Ltd., Shenyang 110027, China
Abstract：OBJECTIVE To construct docetaxel(DOC) nano-micelles using poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate(PEOz-CHMC, PC).METHODS The critical micelle concentration of PC was measured by the hydrazine fluorescence probe method, and DOC-PC micelles(DOC-micelles, DOC-M) were prepared by the thin-film dispersion method. The particle size,morphology,and encapsulation efficiency of DOC-M were characterized.Drug release of DOC-M was evaluated by the dialysis method.Stability and pH-sensitivity of micelles were investigated by simulating the tumor microenvironment.In vitro inhibitory effect of DOC-M was measured by the MTT method in Hela cells. Cell uptake experiments were performed to investigate the uptake of DOC-M in Hela cells by flow cytometry.RESULTS CMC of PC was 9.26 μg·mL-1(4.63×10-6mol·L-1).The appearance of DOC-M showed a regular spherical shape, and the particle size of DOC-M was less than 130 nm and the size distribution was uniform. The Zeta potential and the encapsulation efficiency of DOC-M were (-7.32±0.98) mV and(80.55±2.44)%, respectively.The results of XRD and IR showed that DOC was successfully encapsulated into micelles. In vitro drug release and fetal bovine serum stability results indicated that both the stability and pH-sensitivity of DOC-M were excellent. The results of cytostatic assay suggested that the cell inhibitory effect of DOC-M was stronger under slightly acidic conditions. Cellular uptake analysis showed that DOC-M had low toxicity and significantly promoted the cellular uptake of drugs.CONCLUSION DOC-M exhibits good stability and pH sensitivity, as well as low toxicity and good drug loading capacity, and is expected to become a good carrier for drug delivery.
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2022, Vol. 57 
