Effect of bilayer cholesterol and surface grafted poly(ethylene glycol) on pH-induced release of contents from liposomes by poly(2-ethylacrylic acid)

Liposomal delivery systems have yet to reach the levels of burst release of drug at a diseased site necessary to achieve high local therapeutic levels. A pH sensitive, triggered release system, is one mechanism which shows great promise, especially for use in low pH environments such as tumor interstitial space and endosomes. The pH-sensitive polymer, poly(2- ethylacrylic acid) (PEAA), has been shown to disrupt liposome membranes and release entrapped contents, dependent on membrane compressibility. By adding cholesterol to lipid bilayers, the pH at which entrapped contents were released was reduced from pH 6.7 for a pure lipid system, to pH 6.0 for a cholesterol-saturated system. This decrease in pH, corresponding to an increase in the degree of protonation (i.e. degree of hydrophobicity), was directly correlated to the increase in the elastic area expansion modulus of the bilayers. These results are presented in terms of a balance between polymer solubility and membrane expansion. In a separate experiment, the inclusion of a PEG barrier (5 mol% PEG-2000-lipid) did not prevent PEAA from inducing contents release. This demonstrates that highly hydrated polymeric layers are not effective barriers for other water soluble polymers, and the results may even point to some association between the two polymers.

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Author David Needham Thomas Lord Department of Mechanical Engineering and Materia ...