Influence of Electrostatic Interactions on the Release
of Charged Molecules from Lipid Cubic Phases
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Abstract
The
release of positive, negative, and neutral hydrophilic drugs
from pH responsive bicontinuous cubic phases was investigated under
varying conditions of electrostatic interactions. A weak acid, linoleic
acid (LA), or a weak base, pyridinylmethyl linoleate (PML), were added
to the neutral monolinolein (ML) in order to form lyotropic liquid-crystalline
(LLC) phases, which are negatively charged at neutral pH and positively
charged at acidic pH. Release studies at low ionic strength (<i>I</i> = 20 mM) and at different pH values (3 and 7) revealed
that electrostatic attraction between a positive drug, proflavine
(PF), and the negatively charged LLC at pH = 7 or between a negative
drug, antraquinone 2-sulfonic acid sodium salt (AQ2S), and the positively
charged LLC at pH = 3 did delay the release behavior, while electrostatic
repulsion affects the transport properties only to some extent. Release
profiles of a neutral drug, caffeine, were not affected by the surface
charge type and density in the cubic LLCs. Moreover, the influence
of ionic strength was also considered up to 150 mM, corresponding
to a Debye length smaller than the LLC water channels radius, which
showed that efficient screening of electrostatic attractions occurring
within the LLC water domains results in an increased release rate.
Four transport models were applied to fit the release data, providing
an exhaustive, quantitative insight on the role of electrostatic interactions
in transport properties from pH responsive bicontinuous cubic phases