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34 A pH-sensitive polymer enhances the specificity and therapeutic efficiency of liposomal DOX in vitro
  1. Dongsheng Yang1,
  2. Xueqin Huang1,
  3. Xi Zhao1,
  4. Jing Li1,
  5. Yao Zhang1,
  6. Songcai Liu2
  1. 1Department of Chemistry and Pharmacy, Zhuhai College of Jilin University, Zhuhai, China
  2. 2College of Animal Science, Jilin University, Changchun, China


Background Lipid nanoparticles (LNPs) were eagerly anticipated as promising delivery systems for cancer drugs due to their biocompatibility and tendency to accumulate in tumor tissues. 3-Methylglutarylated poly (glycidol) (MGluPG) was insert into LNPs to form pH-sensitive polymer-modified liposomes which can delivery doxorubicin (DOX) into tumor cells by membrane fusion under relatively acidic conditions. In this study, we report that MGluPG-modified liposomal DOX can efficiently promote antitumor activity and target binding compared to non-MGluPG-modified liposomes.

Methods Briefly, eggPC, MGluPG, cholesterol and DOTAP were dissolved in chloroform and dried to a thin membrane on a rotary evaporator. The dried lipid mixture was further hydrated in a low-pH solution (6 mM ammonium sulphate, pH 5.5) under a vortex mixer to form polydispersity vesicles. The liposomes were then extruded through a polycarbonate membrane with a pore size of 80 nm to reduce particle size and dialyzed in a neutral buffer (pH 7.4) to establish the pH gradient. DOX was loaded by incubating with preformed liposomes at 60° C for 30 min with intermittent vortexing and finally the mixture was eluted using a Sepharose CL-4B gel-filtration column to remove free DOX.

Results The LNPs synthesized in this procedure had a particle size of 168 ± 10.6 nm and a ζ potential of 5 ± 0.78 mV. Drug encapsulation efficiency (EE) was over 85%, meaning most DOX was encapsulated into the liposomes. The release of MGluPG-modified liposomal DOX in phosphate buffer (pH 5.3) was significantly higher than in PBS (pH 7.4) after 24 hours of incubation at 37° C. The MTT test further demonstrated that the IC50 of MGluPG-modified liposomes induced significantly less cytotoxicity. Data from the inhibition of tumour growth revealed MGluPG-modified liposomal DOX was both safe and inhibited tumor growth efficiently.

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