linoleic-acid and monolinolein

A weak amphiphilic base, pyridinylmethyl linoleate, is blended with monolinolein, yielding mesophases with a pH-induced hexagonal-to-cubic transition at pH ≤ 5.5. We show the potential therapeutic role of this mesophase in treating cancerous tissues exploiting their more acidic pH compared to healthy tissues. In vitro release studies with doxorubicin on HT29 human colon cancer cells show a 10-fold faster release and 3-fold increased efficiency for killing cancer cells at pH 5.5 versus pH 7.4, demonstrating the potential of this strategy in cancer treatment.

Topics: Antineoplastic Agents; Cell Proliferation; Doxorubicin; Drug Carriers; Glycerides; HT29 Cells; Humans; Hydrogen-Ion Concentration; Linoleic Acid; Liquid Crystals

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 = 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.

Topics: Glycerides; Hydrogen-Ion Concentration; Linoleic Acid; Static Electricity

We present a food-grade lyotropic liquid crystal system, capable of responding to pH variations with a reversible switch in both the structure and physical properties. The system, which is composed by monolinolein and linoleic acid (97:3 wt % ratio) in the presence of excess water at 37 °C and 150 mM ionic strength, is specifically designed to reversibly change from a Im3m reverse bicontinuous cubic phase to a H(II) reverse columnar hexagonal phase, when changing the pH from neutral (pH 7) to acidic (pH 2) conditions, to simulate intestine and stomach conditions, respectively. The pH responsiveness is provided by the linoleic acid, which, being a weak acid (pK(a) ≈ 5), is essentially in the deprotonated charged state at pH 7 and mainly protonated and neutral at pH 2, imposing changes in the critical packing parameter (CPP) of the lyotropic liquid crystal. The use of this system as an efficient controlled-release delivery vehicle is demonstrated on the model hydrophilic drug phloroglucinol, by both release and diffusion studies at different pH, as followed by ultraviolet-visible (UV-vis) spectroscopy. The Im3m cubic phase at pH 7 is shown to release 4 times faster than the H(II) phase at pH 2, making this system an ideal candidate for oral administration of drugs for targeted delivery in intestine or colon tracts.

Topics: Diffusion; Drug Delivery Systems; Gastric Mucosa; Glycerides; Hydrogen-Ion Concentration; Linoleic Acid; Liquid Crystals; Phloroglucinol