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Influence of Polymer Size, Liposomal Composition, Surface Charge, and Temperature on the Permeability of pH-sensitive Liposomes Containing Lipid-Anchored poly(2-ethylacrylic Acid)

Influence of Polymer Size, Liposomal Composition, Surface Charge, and Temperature on the Permeability of pH-sensitive Liposomes Containing Lipid-Anchored poly(2-ethylacrylic Acid)

Tingli Lu, Zhao Wang, Yufan Ma, Yang Zhang, Tao Chen

Int J Nanomedicine. 2012;7:4917-26.

PMID: 23028220

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP62607094	Poly(2-ethylacrylic acid)		62607-09-4	Price

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