Interactions between Ionic Cellulose Derivatives Recycled from Textile Wastes and Surfactants: Interfacial, Aggregation and Wettability Studies.

Interactions between polymers (P) and surfactants (S) in aqueous solution lead to interfacial and aggregation phenomena that are not only of great interest in physical chemistry but also important for many industrial applications, such as the development of detergents and fabric softeners. Here, we synthesized two ionic derivatives-sodium carboxymethylcellulose (NaCMC) and quaternized cellulose (QC)-from cellulose recycled from textile wastes and then explored the interactions of these polymers with assorted surfactants-cationic (CTAB, gemini), anionic (SDS, SDBS) and nonionic (TX-100)-commonly used in the textile industry. We obtained surface tension curves of the P/S mixtures by fixing the polymer concentration and then increasing the surfactant concentration. In mixtures where polymer and surfactant are oppositely charged (P-/S+ and P+/S-), a strong association is observed, and from the surface tension curves, we determined the critical aggregation concentration (cac) and critical micelle concentration in the presence of polymer (cmcp). For mixtures of similar charge (P+/S+ and P-/S-), virtually no interactions are observed, with the notable exception of the QC/CTAB system, which is much more surface active than the neat CTAB. We further investigated the effect of oppositely charged P/S mixtures on hydrophilicity by measuring the contact angles of aqueous droplets on a hydrophobic textile substrate. Significantly, both P-/S+ and P+/S- systems greatly enhance the hydrophilicity of the substrate at much lower surfactant concentrations than the surfactant alone (in particular in the QC/SDBS and QC/SDS systems).

Model Catanionic Vesicles from Biomimetic Serine-Based Surfactants: Effect of the Combination of Chain Lengths on Vesicle Properties and Vesicle-to-Micelle Transition.

Mixtures of cationic and anionic surfactants often originate bilayer structures, such as vesicles and lamellar liquid crystals, that can be explored as model membranes for fundamental studies or as drug and gene nanocarriers. Here, we investigated the aggregation properties of two catanionic mixtures containing biomimetic surfactants derived from serine. The mixtures are designated as 12Ser/8-8Ser and 14Ser/10-10Ser, where mSer is a cationic, single-chained surfactant and n-nSer is an anionic, double-chained one (m and n being the C atoms in the alkyl chains). Our goal was to investigate the effects of total chain length and chain length asymmetry of the catanionic pair on the formation of catanionic vesicles, the vesicle properties and the vesicle/micelle transitions. Ocular observations, surface tension measurements, video-enhanced light microscopy, cryogenic scanning electron microscopy, dynamic and electrophoretic light scattering were used to monitor the self-assembly process and the aggregate properties. Catanionic vesicles were indeed found in both systems for molar fractions of cationic surfactant ≥0.40, always possessing positive zeta potentials (ζ = +35-50 mV), even for equimolar sample compositions. Furthermore, the 14Ser/10-10Ser vesicles were only found as single aggregates (i.e., without coexisting micelles) in a very narrow compositional range and as a bimodal population (average diameters of 80 and 300 nm). In contrast, the 12Ser/8-8Ser vesicles were found for a wider sample compositional range and as unimodal or bimodal populations, depending on the mixing ratio. The aggregate size, pH and zeta potential of the mixtures were further investigated. The unimodal 12Ser/8-8Ser vesicles ( ≈ 250 nm, pH ≈ 7-8, ζ ≈ +32 mV and a cationic/anionic molar ratio of ≈2:1) are particularly promising for application as drug/gene nanocarriers. Both chain length asymmetry and total length play a key role in the aggregation features of the two systems. Molecular insights are provided by the main findings.

Drug-Derived Surface-Active Ionic Liquids: A Cost-Effective Way To Expressively Increase the Blood-Stage Antimalarial Activity of Primaquine.

Inspired by previous disclosure of room-temperature ionic liquids derived from primaquine and cinnamic acids, which displayed slightly enhanced blood-stage activity compared to the parent drug, we have now combined this emblematic antimalarial with natural fatty acids. This affords surface-active ionic liquids whose liver-stage antiplasmodial activity is either retained or slightly enhanced, while revealing blood-stage antiplasmodial activity at least one order of magnitude higher than that of the parent compound. These findings open new perspectives towards the cost-effective recycling of classical drugs that are either shelved or in decline, and which is not limited to antimalarial agents.

Formation of catanionic vesicles by threonine-derived surfactants and gemini surfactants based on conventional or serine-derived headgroups: designing versatile and cytocompatible nanocarriers.

In this work, we explore the ability of newly synthesized threonine-derived surfactants to form robust, versatile and cytocompatible catanionic vesicles when mixed with gemini surfactants, as potential effective nanocarriers for biomolecules. The threonine surfactants consist of single-tailed amphiphiles with carboxylate headgroups and varying alkyl tail length, CnThr, where n is the (even) number of tail C atoms, varying from 8 to 16. After an initial characterization of the micellization behavior of the neat CnThr surfactants (at pH = 7 and 12), the dodecyl derivative, C12Thr, was selected as the optimal surfactant to investigate regions of formation of spontaneous catanionic vesicles. Phase behavior studies and microstructural characterization of mixtures involving both conventional bis-quat n-s-n gemini (where n and s are the tail and spacer number of C atoms) and biocompatible serine-derived gemini surfactants were carried out. Light and electron microscopy, dynamic light scattering and zeta potential measurements show spontaneous vesicles indeed form and exhibit versatile features in terms of average size, morphology, polydispersity, surface charge and pH. The toxicological profile of the neat surfactants and C12Thr/gemini vesicles based on MTT assays with a L929 cell line was also evaluated, showing good levels of in vitro cytocompatibility. Overall, the assortment of developed catanionic vesicles offers very attractive physicochemical and biological features to be explored for delivery purposes.

Stimuli-Sensitive Self-Assembled Tubules Based on Lysine-Derived Surfactants for Delivery of Antimicrobial Proteins.

Drug delivery vectors based on amphiphiles have important features such as versatile physicochemical properties and stimuli-responsiveness. Amino acid-based surfactants are especially promising amphiphiles due to their enhanced biocompatibility compared to conventional surfactants. They can self-organize into micelles, vesicles and complex hierarchical structures, such as fibers, twisted and coiled ribbons, and tubules. In this work, we investigated the self-assembly and drug loading properties of a family of novel anionic double-tailed lysine-derived surfactants, with variable degree of tail length mismatch, designated as mLys10 and 10Lysn, where m and n are the number of carbon atoms in the tails. These surfactants form tubular aggregates with assorted morphologies in water that undergo gelation due to dense entanglement, as evidenced by light and electron microscopy. Lysozyme (LZM), an enzyme with antimicrobial properties, was selected as model protein for loading. After the characterization of the interfacial properties and phase behavior of the amphiphiles, the LZM-loading ability of the tubules was investigated, under varying experimental conditions, to assess the efficiency of the aggregates as pH- and temperature-sensitive nanocarriers. Further, the toxicological profile of the surfactants per se and surfactant/LZM hydrogels was obtained, using human skin fibroblasts (BJ-5ta cell line). Overall, the results show that the tubule-based hydrogels exhibit very interesting properties for the transport and controlled release of molecules of therapeutic interest.

Effective cytocompatible nanovectors based on serine-derived gemini surfactants and monoolein for small interfering RNA delivery.

Non-viral gene therapy based on gene silencing with small interfering RNA (siRNA) has attracted great interest over recent years. Among various types of cationic complexation agents, amino acid-based surfactants have been recently explored for nucleic acid delivery due to their low toxicity and high biocompatibility. Monoolein (MO), in turn, has been used as helper lipid in liposomal systems due to its ability to form inverted nonbilayer structures that enhance fusogenicity, thus contributing to higher transfection efficiency. In this work, we focused on the development of nanovectors for siRNA delivery based on three gemini amino acid-based surfactants derived from serine - (12Ser)2N12, amine derivative; (12Ser)2COO12, ester derivative; and (12Ser)2CON12, amide derivative - individually combined with MO as helper lipid. The inclusion of MO in the cationic surfactant system influences the morphology and size of the mixed aggregates. Furthermore, the gemini surfactant:MO systems showed the ability to efficiently complex siRNA, forming stable lipoplexes, in some cases clearly depending on the MO content, without inducing significant levels of cytotoxicity. High levels of gene silencing were achieved in comparison with a commercially available standard indicating that these gemini:MO systems are promising candidates as lipofection vectors for RNA interference (RNAi)-based therapies.

Building on Surface-Active Ionic Liquids for the Rescuing of the Antimalarial Drug Chloroquine.

Ionic liquids derived from classical antimalarials are emerging as a new approach towards the cost-effective rescuing of those drugs. Herein, we disclose novel surface-active ionic liquids derived from chloroquine and natural fatty acids whose antimalarial activity in vitro was found to be superior to that of the parent drug. The most potent ionic liquid was the laurate salt of chloroquine, which presented IC50 values of 4 and 110 nM against a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum, respectively, corresponding to an 11- and 6-fold increase in potency as compared to the reference chloroquine bisphosphate salt against the same strains. This unprecedented report opens new perspectives in both the fields of malaria chemotherapy and of surface-active ionic liquids derived from active pharmaceutical ingredients.

Temperature-responsive self-assembled nanostructures from lysine-based surfactants with high chain length asymmetry: from tubules and helical ribbons to micelles and vesicles.

Stimuli-sensitive self-assembled nanostructures are of great relevance for the templating of nanomaterials and the design of efficient systems for the controlled delivery of molecules. Amino acid-based surfactants often display such fascinating self-assembly due to a combination of molecular features such as critical packing parameter, chirality and H-bonding interactions. Herein, we focus on a family of newly synthesized double-chained alkylcarboxylates derived from l-lysine, and designated by 8Lysn, mLys8, with n, m = 12, 14 and 16, and 12Lys16 and 16Lys12, where the numbers represent the number of C atoms in each hydrocarbon chain. The effects of the chain length asymmetry and structural isomerism of the surfactants on their interfacial properties, thermal behavior and self-assembly in water were investigated by a comprehensive toolbox, including surface tension, DSC, imaging (light microscopy, SEM, TEM and AFM) and SAXS. All the surfactants below their Krafft temperature self-organize into tubular structures of various morphologies (flat structures, twisted and coiled ribbons and hollow tubes), forming hydrogels at low surfactant concentration. Upon the solubilization phase transition, micelles or vesicles are formed depending on the surfactant structure, and the tubule-micelle or tubule-vesicle transition is thermoreversible. A molecular-level rationalization of the observed self-assembly and phase transition features is put forth.

Serine-based gemini surfactants with different spacer linkages: from self-assembly to DNA compaction.

Cationic gemini surfactants have strong potential as compaction agents of nucleic acids for efficient non-viral gene delivery. In this work, we present the aggregation behavior of three novel cationic serine-based gemini surfactants as well as their ability to compact DNA per se and mixed with a helper lipid, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). All the surfactants have a 12-12-12 configuration, i.e. two main 12-carbon alkyl chains linked to the nitrogen atom of the amino acid residue and a 12 methylene spacer, but they differ in the nature of the spacer linkage: for (12Ser)2N12, an amine bond; for (12Ser)2CON12, an amide bond; and for (12Ser)2COO12, an ester bond. Interestingly, while the amine-based gemini aggregates into micelles, the amide and ester ones spontaneously form vesicles, which denotes a strong influence of the type of linkage on the surfactant packing parameter. The size, ζ-potential and stability of the vesicles have been characterized by light microscopy, cryogenic scanning electron microscopy (cryo-SEM) and dynamic light scattering (DLS). The interaction of the gemini aggregates with DNA at different charge ratios and in the absence and presence of DOPE has been studied by DLS, fluorescence spectroscopy and cryo-SEM. All the compounds are found to efficiently compact DNA (complexation > 90%), but relevant differences are obtained in terms of the size, ζ-potential and stability of the lipoplexes formed. Results are rationalized in terms of headgroup differences and the type of aggregates present prior to DNA condensation.

Morphology, thermal behavior, and stability of self-assembled supramolecular tubules from lysine-based surfactants.

Synthetic amino acid-based surfactants possess versatile aggregation properties and are typically more biocompatible and biodegradable than surfactants with conventional headgroups. This opens the possibility of a myriad of specialty applications, namely in pharmaceutics, cosmetics, biomedicine, and nanotemplating chemistry. In this work, we have investigated the interfacial and self-assembling properties in aqueous medium of novel double-chained lysine-based surfactants, with particular focus on the behavior of the dodecyl derivative, 12Lys12. Upon cooling from dilute isotropic micellar solutions, this surfactant crystallizes into micrometer-sized tubular structures that induce gelation of the system. The tubules have been characterized in terms of morphology, assembly process, thermal behavior, and stability, by using differential scanning calorimetry, light and scanning electron microscopy, and deuterium NMR. Possible mechanisms for tubule assembly are discussed, on the basis of surfactant molecular shape, H-bonding and electrostatic interactions, and chirality effects.