Preparation and Characterization of Tetracycline-Mediated Bone-Targeting Conjugate Micelles / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare atorvastatin-loaded tetracycline-PEG-PLGA(TC-PEG-PLGA/ATO) polymeric micelles, and investigate its pharmaceutical characteristics and targeting function in vitro. METHODS: The amphiphilic TC-PEG-PLGA conjugate was synthesized via an esterification reaction and identified by the 1H-NMR. Water insoluble atorvastatin was loaded on TC-PEG-PLGA conjugate micelles via dialysis method. The morphology of TC-PEG-PLGA/ATO micelles was observed under transmission electron microscope. The particle size distribution and Zeta potential of TC-PEG-PLGA/ATO micelles were determined by dynamic light scattering method. The drug loading and encapsulation efficiency were measured by HPLC, and in vitro release behavior was investigated via dialysis method. In vitro cytotoxicity was assessed via MTT assay, and bone-targeting activity was investigated via binding to the hydroxyapatite powder. RESULTS: TC-PEG-PLGA/ATO micelle was prepared successfully, and its particle size and Zeta potential were (47.2±4.7) nm and (-14.25±0.31) mV. The encapsulation efficiency and drug loading rate were(98.2±1.51)% and (8.71±0.23)%, respectively. Moreover, the accumulative release of ATO in vitro was about 70% in 48 h, which indicated that the drug was released slowly from the micelles. In vitro cell evaluation showed that TC-PEG-PLGA conjugate micelles were great biocompatibility with MC3T3-E1 cells within the concentration range of 100-500 μg·mL-1. In vitro targeting performance indicated that the proportion of the TC-PLGA NPs bound to Hap(87.94%) was greater than the bound proportion of PLGA NPs(18.59%). CONCLUSION: The TC-PEG-PLGA/ATO micelles exhibit small partical size and good stability, and significantly increased ATO content in aqueous solution. TC-PEG-PLGA/ATO micelles have good delayed release behavior, safety and binding efficacy to the hydroxyapatite powder.