Probing the mechanism of drug/lipid membrane interactions using Biacore.
Assay conditions were established to screen a panel of drugs for binding to liposome surfaces using a surface plasmon resonance (SPR) biosensor. Drugs were found to bind negligibly or reversibly or were retained on the liposome surface. Cationic amphiphilic drugs fell into the last class and correlated with drugs that induce phospholipidosis in vivo. To a first approximation, a single-site model yielded apparent binding affinities that adequately described a drug's dose-dependent binding to liposome surfaces. Affinities ranged at least 1000-fold within the drug panel. A liposome's drug-binding capacity and affinity depended on both the lipid headgroup and the drug's structure. Although a drug's charge state generally dominated whether or not it remained bound to the liposome, subtle structural differences between members of certain drug families led to them having widely differing binding affinities. A comparison between the dissociation of drugs from liposome surfaces by Biacore and the lipid retention measurements determined by a parallel artificial membrane permeability assay was drawn. The results from this study demonstrate the potential of using SPR-based assays to characterize drug/liposome-binding interactions.
Abdiche
Yasmina N
YN
Center for Biomolecular Interaction Analysis, University of Utah School of Medicine, Room No. 4A417, 50 N. Medical Drive, Salt Lake City, UT 84132, USA.
Myszka
David G
DG
D000319:Adrenergic beta-Antagonists / Q000737:chemistry; D001665:Binding Sites; D001667:Binding, Competitive; D003891:Desipramine / Q000737:chemistry; D003992:Dibucaine / Q000737:chemistry; D007700:Kinetics; D008064:Lipidoses; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry; D015203:Reproducibility of Results; D020349:Surface Plasmon Resonance / Q000379:methods*; D013499:Surface Properties
D000319:Adrenergic beta-Antagonists; D008055:Lipids; D008081:Liposomes; D004364:Pharmaceutical Preparations; D011433:Propranolol; D003992:Dibucaine; D003891:Desipramine