title: Interaction of cationic drugs with liposomes.
abstract: 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.
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, Florida 32611, USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Howell
authors.forename: Anuj
authors.initials: A
authors.lastname: Chauhan
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000928:Antidepressive Agents / Q000737:chemistry; D002045:Bupivacaine / Q000737:chemistry; D002412:Cations / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008956:Models, Chemical; D009994:Osmolar Concentration; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D015203:Reproducibility of Results; D012492:Salts / Q000737:chemistry; D055672:Static Electricity; D013499:Surface Properties; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: D000180:Acrylic Resins; D000928:Antidepressive Agents; D002412:Cations; D008051:Lipid Bilayers; D008081:Liposomes; D004364:Pharmaceutical Preparations; D010715:Phosphatidylglycerols; D011109:Polymethacrylic Acids; D012492:Salts; D053835:Unilamellar Liposomes; C030613:polymethacrylic acid; C006903:carbopol 940; C002773:dimyristoylphosphatidylglycerol; D002045:Bupivacaine