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Diacyl glycerol arginine-based surfactants: biological and physicochemical properties of catanionic formulations

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Abstract

In this paper, we report on a catanionic vesicles-based strategy to reduce the cytotoxicity of the diacyl glycerol arginine-based synthetic surfactants 1,2-dimyristoyl-rac-glycero-3-O-(N α-acetyl-l-arginine) hydrochloride (1414RAc) and 1,2-dilauroyl-rac-glycero-3-O-(N α-acetyl-l-arginine) hydrochloride (1212RAc). The behavior of these surfactants was studied either as pure components or after their formulation as pseudo-tetra-chain catanionic mixtures with phosphatidylglycerol (PG) and as cationic mixtures with 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) used as control. The antimicrobial activity of the negatively charged formulations against Acinetobacter baumannii was maintained with respect to the surfactant alone, while a significant improvement of the antimicrobial activity against Staphylococcus aureus was observed, together with a strong decrease of hemolytic activity. The influence of the net charge of the catanionic vesicles on membrane selectivity was studied using model membranes. The dynamics of surface tension changes induced by the addition of 1414RAc/PG aqueous dispersions into phospholipid monolayers composed of zwitterionic DPPC as model system for mammalian membranes and of negatively charged PG mimicking cytoplasmic membrane of Gram-positive bacteria was followed by tensiometry. Our results constitute a proof of principle that tuning formulation can reduce the cytotoxicity of many surfactants, opening their possible biological applications.

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Abbreviations

1212R:

1,2-Dilauroyl-glycero-3-O-l-arginine dihydrochloride

1212RAc:

1,2-Dilauroyl-rac-glycero-3-O-(N α-acetyl-l-arginine) hydrochloride

1414R:

1,2-Dimyristoyl-glycero-3-O-l-arginine dihydrochloride

1414RAc:

1,2-Dimyristoyl-rac-glycero-3-O-(N α-acetyl-l-arginine) hydrochloride

DPPC:

1,2-Dipalmitoyl-sn-glycero-3-phosphatidylcholine

HC50 :

Surfactant concentration inducing 50% of hemolysis

HPLC:

High-performance liquid chromatography

MIC:

Minimum inhibitory concentration

PG:

Phosphatidylglycerol

SD:

Standard deviation

OD:

Optical density

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Acknowledgments

We thank the invaluable advice, suggestions, comments and critical reading of the manuscript by Dr. Luís Rivas and Dra. María Fernández-Reyes from the Centro de Investigaciones Biológicas (CIB-CSIC) of Madrid on biological experiments. Financial support from the Spanish Ministry of Science and Innovation (CTQ2007-604091/BQU and CTQ2009-14151-CO2-01) and Generalitat de Catalunya (2009SGR1331) is gratefully acknowledged. We are also grateful to Ms. Imma Carrera for technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Departament de Tecnologia Química i de Tensioactius, Institut de Química Avançada de Catalunya (IQAC), CSIC, Jordi Girona 18-26, 08034, Barcelona, Spain

    Neus Lozano, Lourdes Pérez, Ramon Pons & Aurora Pinazo

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  1. Neus Lozano
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  2. Lourdes Pérez
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  3. Ramon Pons
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  4. Aurora Pinazo
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Correspondence to Aurora Pinazo.

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Lozano, N., Pérez, L., Pons, R. et al. Diacyl glycerol arginine-based surfactants: biological and physicochemical properties of catanionic formulations. Amino Acids 40, 721–729 (2011). https://doi.org/10.1007/s00726-010-0710-4

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  • DOI: https://doi.org/10.1007/s00726-010-0710-4

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