Co-delivery of doxorubicin and P-gp inhibitor by a reduction-sensitive liposome to overcome multidrug resistance, enhance anti-tumor efficiency and reduce toxicity

Jie Tang, Li Zhang, Huile Gao, Yayuan Liu, Qianyu Zhang, Rui Ran, Zhirong Zhang, Qin He
Drug Delivery 2016, 23 (4): 1130-43
To overcome multidrug resistance (MDR) in cancer chemotherapy with high efficiency and safety, a reduction-sensitive liposome (CL-R8-LP), which was co-modified with reduction-sensitive cleavable PEG and octaarginine (R8) to increase the tumor accumulation, cellular uptake and lysosome escape, was applied to co-encapsulate doxorubicin (DOX) and a P-glycoprotein (P-gp) inhibitor of verapamil (VER) in this study. The encapsulation efficiency (EE) of DOX and VER in the binary-drug loaded CL-R8-LP (DOX + VER) was about 95 and 70% (w/w), respectively. The uptake efficiencies, the cytotoxicity, and the apoptosis and necrosis-inducing efficiency of CL-R8-LP (DOX + VER) were much higher than those of DOX and the other control liposomes in MCF-7/ADR cells or tumor spheroids. Besides, CL-R8-LP (DOX + VER) was proven to be uptaken into MCF-7/ADR cells by clathrin-mediated and macropinocytosis-mediated endocytosis, followed by efficient lysosomal escape. In vivo, CL-R8-LP (DOX + VER) effectively inhibited the growth of MCF-7/ADR tumor and reduce the toxicity of DOX and VER, which could be ascribed to increased accumulation of drugs in drug-resistant tumor cells and reduced distribution in normal tissues. In summary, the co-delivery of chemotherapeutics and P-gp inhibitors by our reduction-sensitive liposome was a promising approach to overcome MDR, improve anti-tumor effect and reduce the toxicity of chemotherapy.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"