Evaluation of the effect of rifampicin on the biophysical properties of the membranes: Significance for therapeutic and side effects

[Display omitted] •The interactions of rifampicin and macrophage membrane models were evaluated.•Several biophysical techniques were executed to assess drug-membrane interaction.•The results confirm that the interactions of RIF with membranes are more pronounced under in vitro pathological condition...

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Bibliographic Details
Published in:International journal of pharmaceutics 2014-05, Vol.466 (1-2), p.190-197
Main Authors: Pinheiro, Marina, Pisco, Sílvia, Silva, Ana Sofia, Nunes, Cláudia, Reis, Salette
Format: Article
Language:English
Subjects:
1,2-Dipalmitoylphosphatidylcholine - chemistry
Antitubercular Agents - administration & dosage
Antitubercular Agents - chemistry
Cell Membrane - metabolism
Drug-membrane studies
Liposomes
Macrophages, Alveolar - metabolism
Membrane biophysical studies
Membrane models
Models, Biological
Rifampicin
Rifampin - administration & dosage
Rifampin - chemistry
Tuberculosis
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Summary:[Display omitted] •The interactions of rifampicin and macrophage membrane models were evaluated.•Several biophysical techniques were executed to assess drug-membrane interaction.•The results confirm that the interactions of RIF with membranes are more pronounced under in vitro pathological conditions.•This work could lead to the development of new anti-TB drugs with higher efficacy and fewer toxic effects. This work aims to study the biophysical interactions of rifampicin (RIF) with three-dimensional macrophage membrane models, under environments with physiological and pathological relevance. The interaction of RIF with liposomes formed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in different pH values (i.e., 5.0, 6.2 and 7.4) was investigated by several biophysical techniques. The RIF’s membrane concentration was quantified by partition coefficient (Kp) using derivative spectrophotometry. To predict the drug’s location across the membrane, fluorescence quenching studies were performed using liposomes labeled with two different fluorescence probes. The effect of the drug on the biophysical parameters of the membrane was carried out by dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS). The overall results confirm that the interactions of RIF with membranes are pH-dependent, being much more pronounced at the acidic pH. A correlation between the effect of RIF on the biophysical properties of the membranes and the pH was found, which may be useful in the development of novel analogs with higher efficacy and fewer side effects, and also to understand the higher selectivity of RIF to the membranes of the infected cells, as well as its side effects.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2014.03.005