Preparation of high-drug-loading cantharidin polymer micelle delivery system and its anti-breast cancer activity / 中国药科大学学报

ABSTRACT

@#Abstract: The aim of this study was to prepare a high drug-carrying capacity micellar drug delivery system (CTD@Sol) of the polymer zebra tetracycline and to preliminarily investigate the feasibility of this drug delivery system for the treatment of breast cancer. Firstly, CTD@Sol was prepared using sol as the carrier material and CTD as the model drug, and its pharmacological properties such as appearance and morphology, particle size, potential and in vitro release were evaluated. The growth inhibitory and apoptotic effects of CTD@Sol on breast cancer (4T1) cells were investigated by MTT assay and Annexin V-FITC/PI double staining assay; the uptake efficiency of 4T1 to this delivery system was investigated by flow cytometry; and the in vivo tissue distribution of the delivery system and the targeting of tumour tissues were investigated by small animal in vivo imaging technique. The results showed that CTD@Sol appeared as a light pale blue creamy white colour, with an average particle size of (159.73 ± 1.96) nm, a PDI of 0.198 ± 0.006, Zeta potential of –(47.60 ± 1.77) mV, an encapsulation rate of (90.29 ± 1.69)% and a drug loading capacity of (45.00 ± 0. 84)%; the in vitro release and haemolysis experiments showed that the drug release rate of CTD@Sol in acidic environment (pH 5.5) was significantly faster than that in neutral environment (pH 7.4), suggesting that the system is acid-sensitive and has good biosafety under endocytosed pH conditions. Cellular uptake, cytotoxicity and apoptosis experiments showed that CTD@Sol was more lethal to 4T1 cells, and the sol-gel polymer micelles as a drug delivery vehicle could significantly improve the cellular uptake efficiency of the drug; in vivo experiments showed that the delivery system had a significant targeting effect on tumour tissues.In conclusion, this study has successfully produced a CTD@Sol drug delivery system with high drug loading capacity (>45%), good pharmacological performance, strong targeting and biosafety, which has the potential to be used in the treatment of breast cancer.