Influence of polymer size, liposomal composition, surface charge, and temperature on the permeability of pH-sensitive liposomes containing lipid-anchored poly(2-ethylacrylic acid)

Abstract

Background

Liposomes containing pH-sensitive polymers are promising candidates for the treatment of tumors and localized infection. This study aimed to identify parameters influencing the extent of contents release from poly(ethylacrylic acid) (PEAA) vesicles, focusing on the effects of polymer size, lipid composition, vesicle surface charge, and temperature.

Methods

Anchored lipid pH-sensitive PEAA was synthesized using PEAA with a molecular weight of 8.4 kDa. PEAA vesicles were prepared by insertion of the lipid-anchored PEAA into preformed large unilamellar vesicles. The preformed liposomes were manipulated by varying the phosphocholine and cholesterol content, and by adding negative or positive charges to the liposomes. A calcein release assay was used to evaluate the effects of polymer size, liposome composition, surface charge, and temperature on liposomal permeability.

Results

The release efficiency of the calcein-entrapped vesicles was found to be dependent on the PEAA polymer size. PEAA vesicles containing a phosphatidylcholine to cholesterol ratio of 60:40 (mol/mol) released more than 80% of their calcein content when the molecular weight of PEAA was larger than 8.4 kDa. Therefore, the same-sized polymer of 8.4 kDa was used for the rest of study. The calcein release potential was found to decrease as the percentage of cholesterol increased and with an increase in the phosphocholine acyl chain length (DMPC DPPC DSPC). Negatively charged and neutral vesicles released similar amounts of calcein, whereas positively charged liposomes released a significant amount of their contents. pH-sensitive release was dependent on temperature. Dramatic content release was observed at higher temperatures.

Conclusion

The observed synergistic effect of pH and temperature on release of the contents of PEAA vesicles suggests that this pH-sensitive liposome might be a good candidate for intracellular drug delivery in the treatment of tumors or localized infection.

Keywords:

• liposomes
• pH-sensitive
• PEAA
• liposomal permeability

Acknowledgments

This paper was supported by the National Basic Research Program of China (973 Program, 2012CB619101) and the Natural Science Foundation of Shaanxi Province (2010JM2021). Ting Chen from the School of Life Science, Northwestern Polytechnical University, is acknowledged for her kind help in preparation of the figures accompanying this manuscript. We gratefully acknowledge Feng Xu from Harvard-MIT Health Science and Technology, Boston, MA, for his kind help with English language.

Disclosure

The authors report no conflicts of interest in this work.