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Interaction of antiinflammatory drugs with EPC liposomes: calorimetric study in a broad concentration range.

Abstract：

:Isothermal titration calorimetry was used to characterize and quantify the partition of indomethacin and acemetacin between the bulk aqueous phase and the membrane of egg phosphatidylcholine vesicles. Significant electrostatic effects were observed due to binding of the charged drugs to the membrane, which implied the use of the Gouy-Chapman theory to calculate the interfacial concentrations. The binding/partition phenomenon was quantified in terms of the partition coefficient (K(p)), and/or the equilibrium constant (K(b)). Mathematical expressions were developed, either to encompass the electrostatic effects in the partition model, or to numerically relate partition coefficients and binding constants. Calorimetric titrations conducted under a lipid/drug ratio >100:1 lead to a constant heat release and were used to directly calculate the enthalpy of the process, DeltaH, and indirectly, DeltaG and DeltaS. As the lipid/drug ratio decreased, the constancy of reaction enthalpy was tested in the fitting process. Under low lipid/drug ratio conditions simple partition was no longer valid and the interaction phenomenon was interpreted in terms of binding isotherms. A mathematical expression was deduced for quantification of the binding constants and the number of lipid molecules associated with one drug molecule. The broad range of concentrations used stressed the biphasic nature of the interaction under study. As the lipid/drug ratio was varied, the results showed that the interaction of both drugs does not present a unique behavior in all studied regimes: the extent of the interaction, as well as the binding stoichiometry, is affected by the lipid/drug ratio. The change in these parameters reflects the biphasic behavior of the interaction-possibly the consequence of a modification of the membrane's physical properties as it becomes saturated with the drug.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Matos C,Lima JL,Reis S,Lopes A,Bastos M

doi

10.1016/S0006-3495(04)74170-3

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

946-54

issue

2

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(04)74170-3

journal_volume

86

pub_type

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