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The growing demand for efficient chemotherapy in many cancers requires novel approaches in target-delivery technologies. Nanomaterials with pH-responsive behavior appear to have potential ability to selectively release the encapsulated molecules by sensing the acidic tumor microenvironment or the low pH found in endosomes. Likewise, polyethylene glycol (PEG)- and poloxamer-modified nanocarriers have been gaining attention regarding their potential to improve the effectiveness of cancer therapy. In this context, DOX-loaded pH-responsive nanoparticles (NPs) modified with PEG or poloxamer were prepared and the effects of these modifiers were evaluated on the overall characteristics of these nanostructures. Chitosan and tripolyphosphate were selected to form NPs by the interaction of oppositely charged compounds. A pH-sensitive lysine-based amphiphile (77KS) was used as a bioactive adjuvant. The strong dependence of 77KS ionization with pH makes this compound an interesting candidate to be used for the design of pH-sensitive devices. The physicochemical characterization of all NPs has been performed, and it was shown that the presence of 77KS clearly promotes a pH-triggered DOX release. Accelerated and continuous release patterns of DOX from CS-NPs under acidic conditions were observed regardless of the presence of PEG or poloxamer. Moreover, photodegradation studies have indicated that the lyophilization of NPs improved DOX stability under UVA radiation. Finally, cytotoxicity experiments have shown the ability of DOX-loaded CS-NPs to kill HeLa tumor cells. Hence, the overall results suggest that these pH-responsive CS-NPs are highly potent delivery systems to target tumor and intracellular environments, rendering them promising DOX carrier systems for cancer therapy.

The encapsulation of antitumor drugs in nanosized systems with pH-sensitive behavior is a promising approach that may enhance the success of chemotherapy in many cancers. The nanocarrier dependence on pH might trigger an efficient delivery of the encapsulated drug both in the acidic extracellular environment of tumors and, especially, in the intracellular compartments through disruption of endosomal membrane. In this context, here we reported the preparation of chitosan-based nanoparticles encapsulating methotrexate as a model drug (MTX-CS-NPs), which comprises the incorporation of an amino acid-based amphiphile with pH-responsive properties (77KS) on the ionotropic complexation process. The presence of 77KS clearly gives a pH-sensitive behavior to NPs, which allowed accelerated release of MTX with decreasing pH as well as pH-dependent membrane-lytic activity. This latter performance demonstrates the potential of these NPs to facilitate cytosolic delivery of endocytosed materials. Outstandingly, the cytotoxicity of MTX-loaded CS-NPs was higher than free drug to MCF-7 tumor cells and, to a lesser extent, to HeLa cells. Based on the overall results, MTX-CS-NPs modified with the pH-sensitive surfactant 77KS could be potentially useful as a carrier system for intracellular drug delivery and, thus, a promising targeting anticancer chemotherapeutic agent.

A general understanding of interactions between DNA and oppositely charged compounds forms the basis for developing novel DNA-based materials, including gel particles. The association strength, which is altered by varying the chemical structure of the cationic cosolute, determines the spatial homogeneity of the gelation process, creating DNA reservoir devices and DNA matrix devices that can be designed to release either single- (ssDNA) or double-stranded (dsDNA) DNA. This review covers recent developments on the topic of DNA gel particles formed in water-water emulsion-type interfaces. The degree of DNA entrapment, particle morphology, swelling/dissolution behavior and DNA release responses are discussed as functions of the nature of the cationic agent used. On the basis of designing DNA gel particles for therapeutic purposes, recent studies on the determination of the surface hydrophobicity and the hemolytic and the cytotoxic assessments of the obtained DNA gel particles have been also reported.

In this investigation, a novel coating for viscose fabric surface modification was developed using a synergistic formulation between a natural antimicrobial cationic surfactant from lysine (MKM) and a biopolymer hyaluronic acid (HA). The interaction between MKM and HA in aqueous solutions, as well as the interactions between their synergistic formulation (HA-MKM) and viscose fabric (CV) were studied using pH-potentiometric titrations', turbidity measurements, the Kjeldahl method for the determination of nitrogen amounts, attenuated total reflectance fourier transform infrared spectroscopy, and scanning electron microscopy. The hydrophilic and antimicrobial properties of the functionalised CV were examined in order to evaluate its usages for medical applications. The results of the interaction studies showed that MKM and HA interact with each other by forming a precipitate when the binding sites of HA are saturated. The precipitate has a slightly positive charge at neutral pH due to excess binding of the MKM to HA. The excess positive charge was also detected on CV coated with HA-MKM. This was proven to be very beneficial for the antimicrobial properties of the functionalised CV. The antimicrobial tests showed exceptional antimicrobial activity of the functionalised CV against Escherichia Coli, Staphylococcus Aureus, Streptococcus Agalactiae, Candida Albicans, and Candida Glabrata, making the CV fabric highly interesting for potential use in medicine. © 2014 Springer Science+Business Media Dordrecht.

In this review, we report the most important contributions in the structure, synthesis, physicochemical (surface adsorption, aggregation and phase behaviour) and biological properties (toxicity, antimicrobial activity and biodegradation) of Gemini natural amino acid-based surfactants, and some potential applications, with an emphasis on the use of these surfactants as non-viral delivery system agents. Gemini surfactants derived from basic (Arg, Lys), neutral (Ser, Ala, Sar), acid (Asp) and sulphur containing amino acids (Cys) as polar head groups, and Geminis with amino acids/peptides in the spacer chain are reviewed. © 2013 Elsevier B.V.

Physicochemical characteristics of cationic vesicular systems prepared from biocompatible diacyl glycerol-arginine surfactants are investigated. These systems form stable cationic vesicles by themselves and the average diameter of the vesicles decreases as the alkyl chain length of the surfactant increases. The addition of DPPC also modifies the physicochemical properties of these vesicles. Among the drugs these cationic formulations can encapsulate, we have considered Ciprofloxacin and 5-Fluorouracil (5-FU). We show that the percentage of encapsulated drug depends on both the physicochemical properties of the carrier and the type of drug. The capacity of these systems to carry different molecules was evaluated performing in vitro drug release studies. Finally, the antimicrobial activity of empty and Ciprofloxacin-loaded vesicles against Gram-positive and Gram-negative bacteria has been determined. Three bacteria were tested: Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. The in vitro drug release from all formulations was effectively delayed. Empty cationic vesicles showed antimicrobial activity and Ciprofloxacin-loaded vesicles showed similar or higher antimicrobial activity than the free drug solution. These results suggest that our formulations represent a great innovation in the pharmaceutical field, due to their dual pharmacological function: one related to the nature of the vehiculated drug and the other related to the innate antibacterial properties of the surfactant-based carriers. © 2014 Elsevier B.V.

As petroleum feedstock decreases, the development of new renewable bio-based and efficient chemicals has attracted more and more interest. Recently, a natural polydisperse polysaccharide named inulin has gained considerable attention. This polysaccharide extracted from chicory roots consists mainly of ß(2-1)-fructosyl furanose units, and has unique properties due to its linear structure and its rather low molecular weight range in comparison to other polysaccharides such as cellulose and starch. This relatively small polymer has focused special interest when several hydrophobic chains are attached on its backbone [1]. This hydrophobically modified inulin (HMI) is able to stabilize many dipersed systems such as o/w emulsions, solid dispersions or films by steric stabilization mechanisms [1]. Additionally, it possesses other important properties like surface activity comparable to those of molecular surfactants or thermo-reversible associative behaviour in aqueous solutions. Also, the hydrophobic groups grafted onto the polyfructose backbone tend to aggregate in order to limit their contact with the solvent leading to the formation of stable coreshell soft nanoparticles [2]. In the present work, we explore the interaction of these macromolecular structures with a wellknown vesicle forming cationic surfactant, didodecyldimethylammonium bromide (DDAB). Initially, one could expect that HMI would stabilize vesicles by the already described steric stabilization mechanisms, but surprisingly this is not the case. Helped by characterization techniques, we have elucidated the nature of these polymer-surfactant interactions by proposing interaction models for surface tension, zero-shear viscosity and SAXS profiles. Here, we present our results with several synthesized HMIs [3] together with pristine inulin (without hydrophobic modifications) and Inutec®SP1 (commercial HMI) for comparative reasons, and we propose some possible applications for these interesting mixed micelles fo

Cationic colloidal systems composed of arginine based surfactants (single or gemini structures) and membrane additive compounds such as DLPC or cholesterol have been characterized by means of size distribution and zeta-potential measurements. The single or monocatenary surfactant (LAM) as well as the gemini with the shortest spacer chain (C6(LA)2) formed micelles, while aqueous solutions of pure gemini surfactants with longer spacers (C9(LA)2 and C12(LA)2) formed very big aggregates. The addition of phospholipids or cholesterol changed drastically the aggregation behaviour. In the case of LAM and C 6(LA)2, the incorporation of additives gave rise to the formation of cationic vesicles. For C9(LA)2 and C 12(LA)2, this type of additives promoted the formation of smaller aggregates. All the formulations had positive zeta-potential values and in general exhibited high colloidal stability. We also evaluated the hemolysis and the antimicrobial activity of these systems. The capability of disrupting erythrocyte membranes depends on the hydrophobicity of the molecules and the size of aggregates in the solution. Gemini surfactants with short spacer chains are more hemolytic than their single chain homologue, while gemini surfactants with long spacers are much less hemolytic than their single chain counterpart. Moreover, for the same formulation, the hemolysis depends on the initial concentration of the stock solution used to set up the hemolysis/concentration curve. Results show that small aggregates interact easily with these biological membranes. The alkyl spacer chain and the presence of additives also play an important role in the antimicrobial activity, and, in general, the interaction with bacteria and erythrocytes is affected by the same parameters. The physico-chemical and biological characterization of these systems might be important for several biotechnological applications in which cationic vesicular systems are involved. © The Royal Society of Chemistry 2013.

Lipoplexes constituted by plasmid DNA pEGFP-C3 (pDNA) or linear double-stranded calf thymus DNA (ctDNA) and mixed cationic liposomes consisting of several percentages of the cationic lysine derived lipid C6(LL)2 and the zwitterionic lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) have been analyzed by both experimental and theoretical approaches. Experimental studies, consisting of electrophoretic mobility/zeta potential, small angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (cryo-TEM), negatively stained transmission electron microscopy (NS-TEM), and GelRed f1uorescence intercalation assays, have been carried out at several liposome and lipoplex compositions, defined in terms of cationic lipid molar fraction and either the mass or charge ratios of the lipoplex. The electrochemical study confirms that, in the presence of the mixed lipids and in contrast with what has usually been found for linear DNA, the plasmid DNA is compacted with a large number of its Na+ counterions, thus yielding a much lower effective negative charge (q pDNA) than that for ctDNA (q ctDNA), as reported recently by us (J. Am. Chem. Soc., 2011) for other lipoplexes. This finding is revealed as crucial for an optimum and efficient lipoplex preparation, since a lower effective negative charge implies a lower quantity of cationic lipid and, accordingly, a potential lower cytotoxicity. TEM experiments reveal a complex scenario of multilamellar nanostructures, from ribbon-type (typically present for chiral lipids) to cluster-type structures (usually found in cationic lipid/ DOPE systems), the composition of the mixed liposome playing an important role in the final morphology of the lipoplex. SAXS diffractograms confirm the existence of these two types of multilamellar structures through a deconvolution process of the first peak of diffractograms into two overlapping bands. On the other hand, a theoretical complexation model is employed to determine the net charge, Ministerio de Ciencia e Innovación (España), Junta de Andalucía, Universidad Complutense de Madrid, Depto. de Química Física, Fac. de Ciencias Químicas, TRUE, pub

In search of more effective and lower impact surfactants, hydrophobic modification of polymers has emerged as a promising strategy for the substitution of low molecular weight surfactants. Inulin, a polysaccharide obtained from chicory roots, has links with the sustainable chemistry model. Furthermore, hydrophobically modified inulins (HMI) can be synthesized in aqueous media. This article reports on the surface activity and aggregation of several compounds with differences in hydrophobic alkyl length and backbone linkage. HMI significantly reduces (down to 30 mN m-1) water surface tension while inulin does not. Both inulins and HMI are shown to aggregate hierarchically at three levels, namely aggregates (<20 nm), flocks (<100 nm) and precipitates (>500 nm). The smaller aggregates, which in the case of inulins can be classified as monomers and in the case of HMI as micelles, have dimensions below 15 nm. The second level of aggregation corresponds to loose flocks with dimensions up to 100 nm and the third level corresponds to the precipitate constituted by aggregation of the flocks. Temperature and basic conditions affect the flock formation and kinetics without a strong influence on the smaller aggregates structure and size. Long term standing of both HMI and inulin solutions eventually precipitates. This precipitate may occupy a large volume but corresponds to a small amount of the solute. In the case of inulins, the precipitate has been found to have a degree of crystallinity that diminishes with increasing temperature.

The toxicity and environmental behavior of new pH-sensitive surfactants from lysine are presented. Three different chemical structures are studied: surfactants with one amino acid and one alkyl chain, surfactants with two amino acids on the polar head and one alkyl chain, and gemini surfactants. The pH sensitivity of these compounds can be tuned by modifying their chemical structures. Cytotoxicity has been evaluated using erythrocytes and fibroblast cells. The toxic effects against these cells depend on the hydrophobicity of the molecules as well as their cationic charge density. The effect of hydrophobicity and cationic charge density on toxicity is different for each type of cells. For erythrocytes, the toxicity increases as hydrophobicity and charge density increases. Nevertheless, for fibroblasts cationic charge density affects cytotoxicity in the opposite way: the higher charge density, the lower the toxicity. The effect of the pH on hemolysis has been evaluated in detail. The aquatic toxicity was established using Daphnia magna . All surfactants yielded EC(50) values considerably higher than that reported for cationic surfactants based on quaternary ammonium groups. Finally, their biodegradability was evaluated using the CO(2) headspace test (ISO 14593). These lysine derivatives showed high levels of biodegradation under aerobic conditions and can be classified as "readily biodegradable compounds".

Lipoplexes constituted by plasmid DNA pEGFP-C3 (pDNA) or linear double-stranded calf thymus DNA (ctDNA) and mixed cationic liposomes consisting of several percentages of the cationic lysine derived lipid C 6(LL)2 and the zwitterionic lipid 1,2-dioleoyl-sn-glycero- 3-phosphoethanolamine (DOPE) have been analyzed by both experimental and theoretical approaches. Experimental studies, consisting of electrophoretic mobility/zeta potential, small angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (cryo-TEM), negatively stained transmission electron microscopy (NS-TEM), and GelRed f1uorescence intercalation assays, have been carried out at several liposome and lipoplex compositions, defined in terms of cationic lipid molar fraction and either the mass or charge ratios of the lipoplex. The electrochemical study confirms that, in the presence of the mixed lipids and in contrast with what has usually been found for linear DNA, the plasmid DNA is compacted with a large number of its Na+ counterions, thus yielding a much lower effective negative charge (q-pDNA) than that for ctDNA (q-ctDNA), as reported recently by us (J. Am. Chem. Soc., 2011) for other lipoplexes. This finding is revealed as crucial for an optimum and efficient lipoplex preparation, since a lower effective negative charge implies a lower quantity of cationic lipid and, accordingly, a potential lower cytotoxicity. TEM experiments reveal a complex scenario of multilamellar nanostructures, from ribbon-type (typically present for chiral lipids) to cluster-type structures (usually found in cationic lipid/DOPE systems), the composition of the mixed liposome playing an important role in the final morphology of the lipoplex. SAXS diffractograms confirm the existence of these two types of multilamellar structures through a deconvolution process of the first peak of diffractograms into two overlapping bands. On the other hand, a theoretical complexation model is employed to determine the net charg

Three different sets of cationic surfactants from lysine have been designed and synthesised. The structure, the number of cationic charges on the polar head and the type of cationic charges were systematically varied in these compounds. The first group consists of three monocatenary surfactants with one lysine as the cationic polar head with one cationic charge. The second group consists of three monocatenary surfactants with two amino acids as cationic polar head with two positive charges. Finally, four gemini surfactants were synthesized in which the spacer chain and the number and type of cationic charges have been regulated. In these work we have studied the influence of the pH on the cationic charge of these molecules and the toxicity of these compounds against two types of human cells: fibroblasts and erythrocytes. We have also determined the effect of the pH on the haemolysis of these compounds. Moreover the aquatic toxicity as well as the biodegradation has been evaluated. The obtained pKa values for these surfactants go from 8.8 to 4.8, these means that they have weak acid properties; consequently the cationic character depends on the pH. The critical micelle concentration of these surfactants was dependent only on the hydrophobic character of the molecules. Overall, all the cationic surfactants synthesized from lysine showed low haemolytic character. The haemolytic activity also depended strongly on the type of structure (monocatenary or geminal) and on the location of the cationic charge. The monocatenary compounds showed higher HC50 values than the Gemini ones, and the haemolytic activity increased significantly in compounds with the positive charge on the trimethylated amino group of the lysine. Finally, all prepared compounds can be considered ready biodegradable surfactants. The percentage of biodegradation is mainly affected by the chemical structure type and not by the cationic charge intensity.

Surfactants are one of the most representative chemical products which are consumed in large quantities every day on a worldwide scale. The use of surfactants in everyday life is almost unavoidable. The development of less irritant, less toxic, consumer-friendly surfactants or surfactant systems is, therefore, of general interest. During the last 20 years, our group has been developing new biocompatible surfactants derived from amino acids. Among them, arginine derivative surfactants constitute a novel class that can be regarded as an alternative to conventional cationic surfactants due to their multifuncional properties and the renewable source of raw materials used during the synthesis process. These characteristics make them candidates of choice as additives in pharmaceutical, food and cosmetic formulations. Evaluation of the irritant potential in vivo, of new products or ingredients, for pharmaceutical use, is required by law in most EU countries, prior to human exposure. However, due to increasing concern over animal use and in lights of its potential ban in the near future, alongside with the obvious ethical implications of using directly human subjects, in vitro alternative methods should now be encouraged. This review reports on the relationship between the structure and toxicity evaluated by in vitro methods of a series of arginine-based surfactants including surfactants with one single chain, gemini surfactants, and surfactants with glycerolipid-like structure.

Medium and long chain esters of inulin have been prepared by reaction of alkenyl succinic anhydrides (ASA) such as 2-octen-1-ylsuccinic anhydride (OSA), and 2-dodecen-1-ylsuccinic anhydride (DDSA) in aqueous media and aqueous surfactant media, respectively. The design of the chemical process was based on the study of the influence of several reaction parameters on reaction efficiency (estimated by 1H NMR analysis of the pure end product) and reaction time. Inulin concentration, pH range, temperature, and the addition of a cationic surfactant such as dodecyltrimethylammonium bromide (DTAB) to the reaction media were evaluated for both OSA and DDSA anhydrides. Inulin slurry aqueous systems were found the best reaction media to carry out the esterification with OSA. In case of DDSA, the addition of a cationic surfactant such as DTAB was required to convert 65% of anhydride. Inulin precipitation was prevented at pH range 8.5-9.0 by the addition of DTAB. The reaction time for the synthesis of dodecenyl succinic esters of inulin, estimated as the total time required to consume all DDSA, was reduced dramatically from 24 h (without DTAB) to less than 1 h in presence of cationic surfactant. The use of micellar basic catalysis resulted in a useful way to obtain long chain alkenyl succinic esters of inulin.

Surfactants are chemical products consumed in large quantities every day on a worldwide scale. The development of less irritant, less toxic, consumer-friendly surfactants is, therefore, of general interest. Amino-acid-based surfactants constitute a novel class of surfactants produced from renewable raw materials and can be seen as an alternative to conventional surfactants. With the aim of testing their applicability in formulations for pharmaceutical, food, and cosmetic industries we have carried out exhaustive studies to elucidate their properties as surfactants. We considered amino acid-based surfactants with one single chain, cystine or arginine gemini surfactants, lysine derivatives, and surfactants with glycerolipid-like structure.

Three different sets of cationic surfactants from lysine have been synthesized. The first group consists of three monocatenary surfactants with one lysine as the cationic polar head with one cationic charge. The second consists of three monocatenary surfactants with two amino acids as cationic polar head with two positive charges. Finally, four gemini surfactants were synthesized in which the spacer chain and the number and type of cationic charges have been regulated. The micellization process, antimicrobial activity, and hemolytic activity were evaluated. The critical micelle concentration was dependent only on the hydrophobic character of the molecules. Nevertheless, the antimicrobial and hemolytic activities were related to the structure of the compounds as well as the type of cationic charges. The most active surfactants against the bacteria were those with a cationic charge on the trimethylated amino group, whereas all of these surfactants showed low hemolytic character.

[Purpose] The purpose of this investigation is the evaluation of the inhibitive performance of a new "gemini" surfactant in the series of bis-quat: N, N, N′, N″, N″-pentamethyl diethyleneamine-N, N″-di-[tetradecylammonium bromide] on the corrosion of iron in 1 M HCl by gravimetric, potentiodynamic and electrochemical impedance measurements. The effect of the temperature on the corrosion behavior of iron in 1 M HCl without and with inhibitor is studied in the temperature range (298-333 K). This work also attempts to correlate thermodynamic and kinetic parameters with the inhibition effect., [Design/methodology/approach] The inhibition efficiency of gemini synthesized is investigated by weight loss, potentiodynamic polarization and impedance spectroscopy methods., [Findings] The synthesized gemini bis-quat acted as a good inhibitor in 1 M HCl, and inhibition efficiency increased with inhibitor concentration and temperature. Polarization curves showed that the surfactant was a mixed-type inhibitor in hydrochloric acid. Impedance spectroscopy measurements showed that the inhibitor acted through the formation of a multilayer film at the iron surface. The adsorption of inhibitor on the iron surface obeyed the Langmuir adsorption isotherm equation. The inhibition effect was satisfactorily explained by both thermodynamic and kinetic parameters., [Originality/value] The adsorption of surfactants in the metal surface can markedly change the corrosion resisting property of the metal. So the study of the relation between the adsorption and corrosion inhibition is of a great importance. This was the first attempt to study the inhibition properties of gemini surfactants at the host laboratory.

Surfactants are among the most versatile and widely used excipients in pharmaceuticals. This versatility, together with their pH-responsive membrane-disruptive activity and low toxicity, could also enable their potential application in drug delivery systems. Five anionic lysine-based surfactants which differ in the nature of their counterion were studied. Their capacity to disrupt the cell membrane was examined under a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model for endosomal membranes. The surfactants showed pH-sensitive hemolytic activity and improved kinetics at the endosomal pH range. Low concentrations resulted in negligible hemolysis at physiological pH and high membrane lytic activity at pH 5.4, which is in the range characteristic of late endosomes. With increasing concentration, the surfactants showed an enhanced capacity to lyse cell membranes, and also caused significant membrane disruption at physiological pH. This observation indicates that, at high concentrations, surfactant behavior is independent of pH. The mechanism of surfactant-mediated membrane destabilization was addressed, and scanning electron microscopy studies were also performed to evaluate the effects of the compounds on erythrocyte morphology as a function of pH. The in vitro cytotoxicity of the surfactants was assessed by MTT and NRU assays with the 3T3 cell line. The influence of different types of counterion on hemolytic activity and the potential applications of these surfactants in drug delivery are discussed. The possibility of using pH-sensitive surfactants for endosome disruption could hold great promise for intracellular drug delivery systems in future therapeutic applications.

Surfactants are used as additives in topical pharmaceuticals and drug delivery systems. The biocompatibility of amino acid-based surfactants makes them highly suitable for use in these fields, but tests are needed to evaluate their potential toxicity. Here we addressed the sensitivity of tumor (HeLa, MCF-7) and non-tumor (3T3, 3T6, HaCaT, NCTC 2544) cell lines to the toxic effects of lysine-based surfactants by means of two in vitro endpoints (MTT and NRU). This comparative assay may serve as a reliable approach for predictive toxicity screening of chemicals prior to pharmaceutical applications. After 24-h of cell exposure to surfactants, differing toxic responses were observed. NCTC 2544 and 3T6 cell lines were the most sensitive, while both tumor cells and 3T3 fibroblasts were more resistant to the cytotoxic effects of surfactants. IC(50)-values revealed that cytotoxicity was detected earlier by MTT assay than by NRU assay, regardless of the compound or cell line. The overall results showed that surfactants with organic counterions were less cytotoxic than those with inorganic counterions. Our findings highlight the relevance of the correct choice and combination of cell lines and bioassays in toxicity studies for a safe and reliable screen of chemicals with potential interest in pharmaceutical industry.

The economic importance of cationic surfactants was realized early in 1935, when their bacteriostatic properties were discovered, leading to many commercial products as sanitizing and antiseptic agents, germicides, fungicides, and as components in pharmaceutical and cosmetic formulations. In these latter applications adverse effects may occur causing eye and skin irritation. Therefore it is paramount to develop new surfactants with low toxicity profiles. During the last 20 years, our group has been developing new biocompatible surfactants derived from amino acids. Among them, Lysine derivative surfactants constitute a novel class that can be regarded as an alternative to conventional cationic surfactants. This work reports on the relationship between the structure and adsorption/aggregation properties of ten Lysine-based surfactants including surfactants with one single chain and gemini surfactants. The critical micellar concentration was determined using conductivity and ionic activity (Cl− and H+). The cmc for single chain surfactants are of the same order of magnitude than commercial cationic surfactants. Concerning gemini surfactants, cmc are one order of magnitude smaller than those of single chain surfactants. The phase behavior at medium to high concentration has been studied by Optical polarizing microscopy, Differential Scanning Calorimetry and Small Angle X-Ray Scattering. The results will be discussed in terms of the structure of the compounds and the position of the cationic charge on the molecule. We will show how, apparently small changes in molecule structure have large influence in phase behaviour.

[ES] La presente invención se refiere a una composición formada por un tensioactivo catiónico que es un diacilglicerol derivado de arginina y al menos un fosfolípidos. La estructura de esta composición confiere propiedades antibacterianas y antileishmanicas, con un menor poder hemolítico, por lo que son adecuadas para su uso para la fabricación de un medicamento para el tratamiento de infecciones causadas por bacterias y protozoos., [EN] The present invention relates to a composition consisting of a cationic surfactant, which is a diacylglycerol derived from arginine, and at least one phospholipid. The structure of said composition imparts antibacterial and antileishmaniasis properties, with reduced haemolytic power, making said composition suitable for use in the production of a drug for treating infections caused by bacteria and protozoa.

Formulaciones de lipoaminoácidos catiónicos con menor poder hemolítico basadas en la formación de pares cataniónicos. La presente invención se refiere a una composición formada por un tensioactivo catiónico que es un diacilglicerol derivado de arginina y al menos un fosfolípidos. La estructura de esta composición confiere propiedades antibacterianas y antileishmanicas, con un menor poder hemolítico, por lo que son adecuadas para su uso para la fabricación de un medicamento para el tratamiento de infecciones causadas por bacterias y protozoos.

There is today a strong trend to replace conventional surfactants with more environmentally benign compounds. Manufacturers and consumers demand for novel environmentally friendly surfactants from renewable resources produced by clean and sustainable technologies (bio-based surfactants). The challenge is to and molecules that meet the mildness, biodegradability, as well as performance and cost-benefit requirements. The use of renewable raw materials such as amino acids and vegetable oil derivatives to prepare novel “natural” surfactants is an exciting and attractive research activity to conciliate the sustainable issues with the industrial development.

Surfactants with the cationic functionality based on an amino acid structure have been used to prepare novel biocompatible devices for the controlled encapsulation and release of DNA. We report here the formation of DNA gel particles mixing DNA (either single- (ssDNA) or double-stranded (dsDNA)) with two different single-chain amino acid-based surfactants: arginine-N-lauroyl amide dihydrochloride (ALA) and N(alpha)-lauroyl-arginine-methyl ester hydrochloride (LAM). The degree of DNA entrapment, the swelling/deswelling behavior, and the DNA release kinetics have been studied as a function of both the number of charges in the polar head of the amino acid-based surfactant and the secondary structure of the nucleic acid. Analysis of the data indicates a stronger interaction of ALA with DNA, compared with LAM, mainly attributed to the double charge carried by the former surfactant compared to the singly charged headgroup of the latter species. The stronger interaction with amphiphiles for ssDNA compared with dsDNA suggests the important role of hydrophobic interactions in DNA. Data on the microstructure of the complexes obtained from small-angle X-ray scattering (SAXS) of the particles strongly suggests a hexagonal packing. It was found that, the shorter the lattice parameter, the stronger the surfactant-DNA interaction and the slower the DNA release kinetics. Complexation and neutralization of DNA on the DNA gel particles was confirmed by agarose gel electrophoresis measurements.

Significant advances made by the authors in the field of cationic surfactants derived from arginine and lysine hydrophilic sources of different structure are reviewed. Linear, gemini and glycerolipid-like structures with polar groups consisting of Arg or Lys amino acids are described. Our multidisciplinary approach includes design, synthesis, adsorption at interfaces and self-assembly behavior, antimicrobial activity, and studies of biocompatibility including ecotoxicity, biodegradability and irritation effects. Considering the green chemistry principles, the synthesis contemplates the preparation of more efficient and safer surfactants using renewable raw materials for the synthesis of surfactants: proteins, peptides, amino acids and triacylglycerols, using biocatalysis as condensating methodology, and designing for biodegradation. Also in order to increase the efficiency of these compounds, a complete characterization including self-assembly, ecotoxicity, biodegradability, and studies of mechanisms of toxicity has been carried out. The structure of the surfactant molecule affects micellization and not the nature of the polar head (Arg or Lys). The critical micelle concentrations of the gemini surfactants are three orders of magnitude lower than the linear ones for the same alkyl chain length. The presence of a cationic charge in the amino acid provides antimicrobial activity to these compounds.

Se han preparado como sales clorohidratadas cinco nuevos tensioactivos catiónicos de cadena alquílica C12: dos tensioactivos monocatenarios derivados de arginina y lisina, en los que se ha variado la posición de la carga catiónica en la lisina (grupo ¿-amino ó ¿-amino) y tres tensioactivos geminales derivados de lisina, en los que se ha variado la posición de la carga catiónica (grupo ¿-amino ó ¿-amino de la lisina) y la cadena espaciadora (diamina con 6 grupos metileno o espermidina). Se ha estudiado como influyen estos parámetros estructurales en la concentración micelar crítica (CMC), la actividad hemolítica y la biodegradabilidad de los compuestos. La posición de la carga catiónica en la lisina no influye en la CMC de los tensioactivos sintetizados. Sin embargo, el valor de la CMC de los tensioactivos geminales (en cualquier caso muy inferior al de los monocatenarios) sí se ve afectado por la presencia de la carga positiva debida a la espermidina protonada. Los compuestos monocatenarios presentan escasa actividad hemolítica, que no se ve afectada por la posición de la carga catiónica en la lisina. Los tensioactivos geminales poseen una capacidad hemolítica mayor, que depende de la posición de la carga catiónica y muy especialmente de la carga positiva adicional de la espermidina protonada. La biodegradabilidad aerobia en el medio ambiente acuático sólo se ha evaluado para los tensioactivos monocatenarios. Ambos compuestos han resultado biodegradables y no se ha observado ninguna influencia de la posición de la carga catiónica en la lisina en el porcentaje de biodegradación obtenido.