The Thermodynamics of the Partitioning of Ionizing Molecules Between Aqueous Buffers and Phospholipid Membranes

Austin, Rupert P.; Barton, Patrick; Davis, A. M.; Fessey, Roger E.; Wenlock, Mark C.

doi:10.1007/s11095-005-6336-7

Cited by 28 publications

(25 citation statements)

References 26 publications

(18 reference statements)

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“…The first process, which was observed for concentrations between 15.625 and 500 M, exhibits saturable binding. This process, also reported by others, presumably arises from electrostatic and hydrophobic interactions where the negatively charged phosphate headgroup interacts with the positively charged amine group of the drug while the lipophilic groups align with the hydrophobic carbon chains of the bilayer [6][7][8]. Recent studies have also yielded results consistent with the electrostatic interactions being of paramount importance [9,10].…”

Section: Resultssupporting

confidence: 55%

Characterisation of chlorpromazine binding to lipid bilayer membranes

Nussio

Sykes

Miners

et al. 2006

2006 International Conference on Nanoscience and Nanotechnology

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Abstract-With the aid of Atomic Force Microscopy (AFM) and Surface Plasmon Resonance (SPR), the interaction of chlorpromazine (CPZ) with phosphatidylcholine bilayer membranes was investigated. The interaction of CPZ had inherent effects on the transition temperature (T M ), and hence, fluidity of DMPC phospholipid membranes. It was discovered that CPZ intercalates within the membrane bilayers to form a drug/phospholipid complex.

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Section: Resultssupporting

confidence: 55%

Characterisation of chlorpromazine binding to lipid bilayer membranes

Nussio

Sykes

Miners

et al. 2006

2006 International Conference on Nanoscience and Nanotechnology

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“…This process, also reported by others, presumably arises from electrostatic and hydrophobic interactions whereby the negatively charged phosphate head group interacts with the positively charged amine group of the drug, whereas the lipophilic groups align with the hydrophobic carbon chains of the bilayer. [13][14][15] Recent studies have also yielded results consistent with the electrostatic interactions being of paramount importance. [16,17] The second process may be considered a high-capacity, low-affinity process.…”

Section: Discussionmentioning

confidence: 95%

Characterisation of the Binding of Cationic Amphiphilic Drugs to Phospholipid Bilayers Using Surface Plasmon Resonance

et al. 2007

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The interactions of three cationic amphiphilic drugs (CPZ, AMI, PROP) with phospholipid vesicles comprising DOPC, DMPC, or DSPC were investigated using surface plasmon resonance (SPR). Responses for CAD concentrations in the range 15.625 to 1500 microM were measured. The greatest uptake by each phospholipid bilayer occurred with CPZ. Inclusion of CAD concentrations between 750 and 1500 microM provided evidence for a second nonsaturable binding process, which may arise from intercalation of the drugs within the lipid bilayer. CAD binding was additionally shown to be dependent on membrane fluidity. Responses were initially fitted over a concentration range of 15.625 to 500 microM using a model which incorporated terms for a saturable binding site. This yielded very poor values of K(D) and nonsensible values of saturation responses. Subsequently, responses were fit to the expression for a model which incorporated terms for both a saturable binding site and second nonsaturable site. Measurable binding affinities (K(D) values ranged from 170 to 814 microM) were obtained for DOPC and DMPC bilayers which are similar to values reported previously. This work demonstrates that SPR studies with synthetic phospholipid bilayers provide a potentially useful approach for characterising drug-membrane binding interactions and for providing insight into the processes that contribute to drug-membrane binding.

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“…A comparison between the uptake of opipramol with the uptakes of imipramine and dosulepin illustrate the importance of the electrostatic interactions in drug binding to the anionic, pegylated liposomes. An earlier study by Austin et al21 involving the net neutral, zwitterionic lipid DMPC pointed to a more favorable thermodynamic interaction between the lipid bilayer and charged drugs versus neutral ones. Here, changes in partitioning are compared for charged versus partially uncharged drugs for liposomes composed of a net negative lipid, DOPG.…”

Section: Resultsmentioning

confidence: 97%

Binding of Imipramine, Dosulepin, and Opipramol to Liposomes for Overdose Treatment

Howell

Chauhan

2009

Journal of Pharmaceutical Sciences

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The Thermodynamics of the Partitioning of Ionizing Molecules Between Aqueous Buffers and Phospholipid Membranes

Abstract: The observations are consistent with the notion of there being a favourable electrostatic interaction (enthalpically) between the positively charged amino-group of predominantly cationic compounds and the negatively charged phosphate group of the vesicle.

Cited by 28 publications

References 26 publications

Characterisation of chlorpromazine binding to lipid bilayer membranes

Characterisation of chlorpromazine binding to lipid bilayer membranes

Characterisation of the Binding of Cationic Amphiphilic Drugs to Phospholipid Bilayers Using Surface Plasmon Resonance

Binding of Imipramine, Dosulepin, and Opipramol to Liposomes for Overdose Treatment

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