Diacyl glycerol arginine-based surfactants: biological and physicochemical properties of catanionic formulations.
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.
Lozano
Neus
N
Departament de Tecnologia Química i de Tensioactius, Institut de Química Avançada de Catalunya, CSIC, Jordi Girona 18-26, 08034, Barcelona, Spain.
Pérez
Lourdes
L
Pons
Ramon
R
Pinazo
Aurora
A
D040981:Acinetobacter baumannii / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001120:Arginine / Q000737:chemistry; D002412:Cations / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004075:Diglycerides / Q000737:chemistry; D004912:Erythrocytes / Q000187:drug effects; D053878:Hemolytic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012756:Sheep; D013211:Staphylococcus aureus / Q000187:drug effects; D013500:Surface Tension; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
C011439:1,2-diacylglycerol; D000900:Anti-Bacterial Agents; D002412:Cations; D004075:Diglycerides; D053878:Hemolytic Agents; D013501:Surface-Active Agents; D001120:Arginine