Co-Delivery of Berberine Chloride and Tariquidar in Nanoliposomes Enhanced Intracellular Berberine Chloride in a Doxorubicin-Resistant K562 Cell Line Due to P-gp Overexpression

Abstract

The MDR phenomenon has become a major obstacle in the treatment of cancers, and among the strategies to reverse it, the inhibition of P-gp function and expression is essential to increase for effective anticancer drugs. In the present paper, the co-delivery of berberine chloride and tariquidar loaded nanoliposomes was investigated with the aim of enhancing solubility and improving desired effects for the antineoplastic drug and the P-gp inhibitor. Developed nanoliposomes were loaded with the electron-dense enzyme horseradish peroxidase, and analyzed by TEM to investigate their ability to enter in both K562 and K562/DOXO cell lines. Receptor-mediated endocytosis was evidenced for both cell lines. Nanoliposomes were loaded with tariquidar, berberine chloride, or both, maintaining chemical and physical characteristics—i.e., size, homogeneity, and encapsulation efficiency—and high suitability for parenteral administration. Tariquidar was able to reverse the MDR in the K562/DOXO cell line. Tariquidar- and berberine chloride-loaded nanoliposomes showed a significant increase of berberine chloride accumulation in tumor cells, which could be correlated with resensitization of the resistant cells to the antitumor agent. These results suggest that the co-delivery of the P-gp inhibitor, tariquidar, and the cytotoxicity inducer, berberine chloride, looks like a promising approach to overcome the MDR.

Keywords

• MDR
• berberine chloride
• tariquidar
• nanoliposomes
• endocytosis
• uptake