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Preparation of mitochondrial targeted calcium arsenite/doxorubicin lipid nanoparticles and the in vitro study in reversing tumor drug resistance / 药学学报
Acta Pharmaceutica Sinica ; (12): 3243-3251, 2021.
Article in Chinese | WPRIM | ID: wpr-906845
Responsible library: WPRO
ABSTRACT
This study aims at the critical role of P-glycoprotein (P-gp) in tumor drug resistance, taking advantage of the adenosine triphosphate (ATP) dependence of P-gp mediated drug transport and efflux across the cell membrane. Mitochondrial targeted calcium arsenite/doxorubicin (DOX) lipid nanoparticles were constructed via hydrothermal method and thin-film dispersion method for reversing tumor drug resistance. The results showed that the lipid nanoparticles were uniform in size and well dispersed with a mean particle size of (261 ± 7) nm, zeta potential of (-9.6 ± 1.3) mV. The DOX loading efficiency and encapsulation efficiency were 22.6% and 84.0%. The in vitro drug release profile was pH-dependent; the drug accumulation at mitochondria was significantly increased, which then caused overload of calcium and inhibition of P-gp and ATP, thereby reversing tumor drug resistance. The simultaneously released arsenite ion and DOX could synergistically kill the tumor cells. In summary, the lipid nanoparticles prepared in this study have uniform particle size, high drug loading efficiency and encapsulation efficiency, excellent colloidal stability, pH responsiveness, and impressive ability to reverse tumor drug resistance, which may hold great potential in further clinical applications.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Acta Pharmaceutica Sinica Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Acta Pharmaceutica Sinica Year: 2021 Type: Article