Interaction of Cationic Drugs with Liposomes

• Published in: Langmuir 2009-10, Vol.25 (20), p.12056-12065
• Main Authors: Howell, Brett A, Chauhan, Anuj
• Format: Article
• Language: English
• Subjects: Acrylic Resins - chemistry; Antidepressive Agents - chemistry; Bupivacaine - chemistry; Cations - chemistry; Cations - metabolism; Chemistry; Colloidal state and disperse state; Colloids: Surfactants and Self-Assembly, Dispersions, Emulsions, Foams; Exact sciences and technology; General and physical chemistry; Hydrophobic and Hydrophilic Interactions; Lipid Bilayers - metabolism; Liposomes - chemistry; Liposomes - metabolism; Membranes; Models, Chemical; Osmolar Concentration; Permeability; Pharmaceutical Preparations - chemistry; Pharmaceutical Preparations - metabolism; Phosphatidylglycerols - chemistry; Polymethacrylic Acids - chemistry; Reproducibility of Results; Salts - chemistry; Static Electricity; Surface physical chemistry; Surface Properties; Unilamellar Liposomes - chemistry
• ISSN: 0743-7463; 1520-5827
• DOI: 10.1021/la901644h

Interactions between cationic drugs and anionic liposomes were studied by measuring binding of drugs and the effect of binding on liposome permeability. The measurements were analyzed in the context of a continuum model based on electrostatic interactions and a Langmuir isotherm. Experiments and modeling indicate that, although electrostatic interactions are important, the fraction of drug sequestered in the double-layer is negligible. The majority of drug enters the bilayer with the charged regions interacting with the charged lipid head groups and the lipophilic regions associated with the bilayer. The partitioning of the drug can be described by a Langmuir isotherm with the electrostatic interactions increasing the sublayer concentration of the drug. The binding isotherms are similar for all tricyclic antidepressants (TCA). Bupivacaine (BUP) binds significantly less compared to TCA because its structure is such that the charged region has minimal interactions with the lipid heads once the BUP molecule partitions inside the bilayer. Conversely, the TCAs are linear with distinct hydrophilic and lipophilic regions, allowing the lipophilic regions to lie inside the bilayer and the hydrophilic regions to protrude out. This conformation maximizes the permeability of the bilayer, leading to an increased release of a hydrophilic fluorescent dye from liposomes.