Fluorescence studies on binding of amphiphilic drugs to isolated lamellar bodies: relevance to phospholipidosis

Joshi, Urmila M.; Rao, P. S.; Kodavanti, S.; Lockard, Virginia G.; Mehendale, Harihara M.

doi:10.1016/0005-2760(89)90078-7

Cited by 57 publications

(44 citation statements)

References 43 publications

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“…Of these CADs, CPZ exhibited the greatest uptake with respect to phospholipid interactions, whereas the largest interactions were observed for bilayers comprising DOPC. Previous studies have also demonstrated CPZ to have a greater interaction and thus uptake relative to AMI and PROP, [6,7,[10][11][12] presumably as CPZ is more hydrophobic. [12] Importantly, however, the boundaries of previous work have been extended, as two discrete binding processes were identified.…”

Section: Discussionmentioning

confidence: 99%

“…[6,7] Previous studies using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) phospholipid vesicles and lamellar bodies have also reported two binding affinities for CPZ over the concentration range employed in the current study. [10,18] As noted previously, binding data to 500 mm were modelled with Equation (1). K D values generated ranged from 413 to 1127 mm.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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“…with an *(P particular within lysosomes. Complexation lowers intralysosomal free drug concentration and entails further drug uptake (Liillmann-Rauch, 1979;Joshi et al, 1989). …”

Section: _____/__________________________________mentioning

confidence: 99%

“…lysosomes filled with undegraded PLs (Lullmann et al, 1978). CADs either directly inhibit lysosomal phospholipases (Hostetler et al, 1988) or form undegradable complexes with PLs (Liillmann & Wehling, 1979;Joshi et al, 1989). The formation of drug-PL complexes further enhances intracellular accumulation of drugs (Hein et al, 1990;Reasor, 1991).…”

Section: Introductionmentioning

confidence: 99%

Inhibition by vitamin E of drug accumulation and of phospholipidosis induced by desipramine and other cationic amphophilic drugs in human cultured cells

Scuntaro

Kientsch

Wiesmann

et al. 1996

British J Pharmacology

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1 Cationic amphiphilic drugs (CADs) are widely used in chronic pharmacotherapies in spite of frequently observed side effects connected with lysosomal phospholipid (PL) storage. 2 It has recently been shown that cx-tocopherol (a-Toc) inhibits drug-and PL accumulation in cell cultures chronically exposed to the CAD, amiodarone. 3 The mechanisms of a-Toc action on drug kinetics and PL storage were studied in human cultured fibroblasts exposed to single and repetitive doses of desipramine and other CADs. 4 a-Toc did not influence the initial, pH-dependent rapid phase of drug uptake. It inhibited, in a dosedependent manner, the slow and the cumulative phases of drug uptake and coincidently the accumulation of cellular PLs. 5 The inhibitory effects of c-Toc on CAD and PL accumulations depends on the ratio between CAD and a-Toc concentrations in the medium. This points to competition between a-Toc and CADs for PL complex formation. 6 Effectiveness of a-Toc on drug uptake varies among different CADs. It depends on its structural integrity but is independent of stereoisomerism. The inhibitory action is restricted to the piggyback slow drug uptake and therefore related to the proportion of membrane-mediated transport to permeation into lysosomes (rapid uptake). This proportion differs among CADs. 7 a-Toc prevents lysosomal membrane-PL storage, accelerates disintegration of PL-stores and normalizes drug-related increased membrane fluidity. This strongly suggests that a-Toc restores membrane recycling, impaired by CAD exposure.8 It remains to be tested in vivo whether cx-Toc reduces CAD side effects without interfering with drug effectiveness.

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“…It has only been referred to previously in relation to SPR sensorgrams where a heterogeneous interaction was established [11,12]. Previous studies utilising 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) phospholipid vesicles and lamellar bodies has also reported two binding affinities for CPZ over the concentration range employed in the current study [13,14]. …”

Section: Resultsmentioning

confidence: 90%

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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Fluorescence studies on binding of amphiphilic drugs to isolated lamellar bodies: relevance to phospholipidosis

Cited by 57 publications

References 43 publications

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

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

Inhibition by vitamin E of drug accumulation and of phospholipidosis induced by desipramine and other cationic amphophilic drugs in human cultured cells

Characterisation of chlorpromazine binding to lipid bilayer membranes

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