Biocompatible Catanionic Vesicles from Arginine-Based Surfactants: A New Strategy to Tune the Antimicrobial Activity and Cytotoxicity of Vesicular Systems

Abstract

Their stability and low cost make catanionic vesicles suitable for application as drug delivery systems. In this work we prepared catanionic vesicles using biocompatible surfactants: two cationic arginine-based surfactants (the monocatenary Nα-lauroyl-arginine methyl ester—LAM and the gemini Nα,Nϖ-bis(Nα-lauroylarginine) α, ϖ-propylendiamide—C3(CA)2) and three anionic amphiphiles (the single chain sodium dodecanoate, sodium myristate, and the double chain 8-SH). The critical aggregation concentration, colloidal stability, size, and charge density of these systems were comprehensively studied for the first time. These catanionic vesicles, which form spontaneously after mixing two aqueous solutions of oppositely charged surfactants, exhibited a monodisperse population of medium-size aggregates and good stability. The antimicrobial and hemolytic activity of the vesicles can be modulated by changing the cationic/anionic surfactant ratio. Vesicles with a positive charge efficiently killed Gram-negative and Gram-positive bacteria as well as yeasts; the antibacterial activity declined with the decrease of the cationic charge density. The catanionic systems also effectively eradicated MRSA (Methicillin-resistant Staphylococcus Aureus) and Pseudomonas aeruginosa biofilms. Interestingly, the incorporation of cholesterol in the catanionic mixtures improved the stability of these colloidal systems and considerably reduced their cytotoxicity without affecting their antimicrobial activity. Additionally, these catanionic vesicles showed good DNA affinity. Their antimicrobial efficiency and low hemolytic activity render these catanionic vesicles very promising candidates for biomedical applications.

Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers

“…It was shown that cationic antimicrobial lipopeptides can be effective in the treatment of wound bacterial infection without adverse effects on porcine skin [ 83 ]. Recent studies on antimicrobial arginine-based gemini surfactants indicate an interesting possibility to incorporate them into vesicles together with anionic amphiphiles (catanionic vesicles), resulting in improved selectivity [ 84 ]. On the other hand, cationic micelles and liposomes injected intravenously into rats result in DNA damage in lungs and spleen [ 85 ].…”

Aggregation Behavior, Antibacterial Activity and Biocompatibility of Catanionic Assemblies Based on Amino Acid-Derived Surfactants

“…The ζ-potential value of this formulation is negative and the interaction with the also negatively charged bacterial membrane is hindered. Recent studies revealed that the antibacterial efficiency of catanionic vesicles prepared with gemini arginine-based surfactants depends on the anionic/cationic ratio of the formulations [ 33 ].…”

“…Results obtained in this work agree with those obtained recently for catanionic systems prepared with arginine-based gemini surfactants. In Pinazo et al [ 33 ], it was found that the hemolytic activity of these formulations mainly depended on the proportion of cationic surfactant. Moreover, it was also observed that the incorporation of cholesterol into the catanionic vesicles resulted in a significant decrease in their hemolytic activity.…”

Lipid-Based Nanovesicular Drug Delivery Systems

“…Thus, although catanionic vesicles have a huge applicability in biomedicine, they can suffer safety problems due to their eventual low bio-and emocompatibility. Numerous ongoing researches point to the optimization of their morphology, hydrophobicity, and ionic charge by carefully choosing the proper surfactant and by tuning the anionic/cationic surfactant ratio eventually adding some suited additive [218].…”