Heterogeneous domains and membrane permeability in phosphatidylcholine - Phosphatidic acid rigid vesicles as a function of pH and lipid chain mismatch

Shrirang Karve, Gautam Bajagur Kempegowda, Stavroula Sofou

Research output: Contribution to journalArticlepeer-review

Abstract

Heterogeneous lipid membranes tuned by pH were evaluated at 37 °C in the form of PEGylated vesicles composed of lipid pairs with dipalmitoyl (n = 16) and distearoyl (n = 18) chain lengths. One lipid type was chosen to have the titratable moiety phosphatide acid on its headgroup, and the other lipid type was chosen to have a phosphatidylcholine headgroup. The effect of pH on the formation of lipid heterogeneities and on membrane permeability was studied on vesicles composed of lipid pairs with matching and nonmatching chain lengths. The formation of lipid heterogeneities increases with decreasing pH in membranes composed of lipid pairs with either matching or nonmatching chain lengths. Increased permeability with decreasing pH was exhibited only by membranes composed of lipid pairs with nonmatching chain lengths. Permeability rates correlate strongly with the predicted extent of interfacial boundaries of heterogeneities, suggesting defective packing among nonmatching acyl chains of lipids. In heterogeneous mixtures with one lipid type in the fluid state (n = 12), the dependence of membrane permeability on pH is weaker. In the presence of serum proteins, PEGylated gel-phase vesicles containing lipid pairs with nonmatching chain lengths exhibit faster release rates with decreasing pH compared to measured release rates in phosphate buffer, suggesting a second mechanism of formation of separated phases. PEGylated vesicles composed of lipid pairs with nonmatching chain lengths labeled with internalizing anti-HER2/neu antibodies that target overexpressed antigens on the surface of SKOV3-NMP2 ovarian cancer cells exhibit specific cancer cell targeting, followed by extensive internalization (more than 84% of bound vesicles) and fast release of contents intracellularly. These PEGylated vesicles composed of rigid membranes for long blood circulation times that exhibit pH-dependent release of contents intracellularly could become potent drug delivery carriers for the targeted therapy of solid tumors.

Original languageEnglish (US)
Pages (from-to)5679-5688
Number of pages10
JournalLangmuir
Volume24
Issue number11
DOIs
StatePublished - Jun 3 2008
Externally publishedYes

ASJC Scopus subject areas

  • General Materials Science
  • Condensed Matter Physics
  • Surfaces and Interfaces
  • Spectroscopy
  • Electrochemistry

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