Effects of a novel antimycobacterial compound on the biophysical properties of a pulmonary surfactant model membrane

• The interactions of RFB2 with two- and three-dimensional membrane models of the pulmonary surfactant (PS) were evaluated.
• Several biophysical techniques were executed to assess drug–PS membrane interaction.
• Detailed information at the molecular level was obtained about the pronounced interaction of RFB2 with PS membrane model.
• The interaction of RFB2 with the PS membrane model happens mainly at the head groups level.
• This study may be ultimately applied to the development of liposomes composed of DPPC, as drug delivery systems.

In this work, the interactions of a novel rifabutin's analogue (N′-acetyl-rifabutin, RFB2) with two-dimensional (Langmuir monolayers) and three-dimensional (large unilamellar and multilamellar vesicles) membrane models of the pulmonary surfactant (PS) were evaluated. The main purpose of this study is to obtain detailed information at the molecular level between the interactions of RFB2 with the phospholipids of the PS, under physiological conditions. Therefore, the effects of RFB2 in the monolayer phase behaviour at the air–water interface and in the lipid bilayer of membrane models composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) have been systematically compared. In this context, several biophysical techniques were carried out to establish the interactions of RFB2 with the two-dimensional membrane models of the PS: Langmuir isotherms, Brewster angle microscopy (BAM), and polarization-modulation infrared reflection–absorption spectroscopy (PM-IRRAS); and with three-dimensional membrane models of the PS: derivate spectrophotometry partition coefficient (Kp), dynamic light scattering (DLS), small and wide angle X-ray scattering (SAXS and WAXS).The results gathered by the different biophysical techniques and the PS membrane model used provide detailed information about the strong interactions of RFB2 with the polar head groups of the PS phospholipids and permit to establish the impact of the RFB2-PS membrane interactions, justifying an often unexplored biophysical approach to the drug's pharmacokinetics and toxicological effect.

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