ABSTRACT
HYPOTHESIS: Antimicrobial resistance (AMR) is a pressing global health concern. ESKAPEE pathogens, such as Methicillin-resistant Staphylococcus aureus (MRSA) are notable of concern in healthcare settings due to their resistance to critical antibiotics. To combat AMR, the development of alternatives such as bacterial membrane-active agents is crucial. Fatty acids (FAs) have emerged as a sustainable, antibiotic-free solution with inherent antibacterial activity. However, long chain saturated fatty acids (LCFAs) sodium soaps exhibit poorly antibacterial properties in comparison to short chain FAs, believed to be linked to limited solubility in aqueous media. EXPERIMENTS: We employed choline as a chaotropic organic counter-ion to enhance the solubility of LCFAs and investigated their antibacterial effects against MRSA. The optimal medium conditions for micelle formation for LCFAs was first investigated. Then, we determined the critical micelle concentration (CMC), micellar morphology, and aggregation number through surface tension measurements and small angle neutron scattering experiments. Antimicrobial activity was assessed using minimum bactericidal concentration (MBC) assays and time-kill experiments. FINDINGS: We have identified conditions where LCFAs are effective against MRSA for the first time, providing valuable insights for developing new antibacterial agents to fight AMR. LCFAs need to be used above their Krafft temperatures and CMC to exhibit antibacterial efficacy.
ABSTRACT
The spread of new strains of antibiotic-resistant pathogenic microorganisms has led to the urgent need to discover and develop new antimicrobial systems. The antibacterial effects of fatty acids have been well-known and recognized since the first experiments of Robert Koch in 1881, and they are now used in diverse fields. Fatty acids can prevent the growth and directly kill bacteria by insertion into their membrane. For that, a sufficient amount of fatty acid molecules has to be solubilized in water to transfer from the aqueous phase to the cell membrane. Due to conflicting results in the literature and lack of standardization methods, it is very difficult to draw clear conclusions on the antibacterial effect of fatty acids. Most of the current studies link fatty acids' effectiveness against bacteria to their chemical structure, notably the alkyl chain length and the presence of double bonds in their chain. Furthermore, the solubility of fatty acids and their critical aggregation concentration is not only related to their structure, but also influenced by medium conditions (pH, temperature, ionic strength, etc.). There is a possibility that the antibacterial activity of saturated long chain fatty acids (LCFA) may be underestimated due to the lack of water solubility and the use of unsuitable methods to assess their antibacterial activity. Thus, enhancing the solubility of these long chain saturated fatty acids is the main goal before examining their antibacterial properties. To increase their water solubility and thereby improve their antibacterial efficacy, novel alternatives may be considered, including the use of organic positively charged counter-ions instead of the conventional sodium and potassium soaps, the formation of catanionic systems, the mixture with co-surfactants, and solubilization in emulsion systems. This review summarizes the latest findings on fatty acids as antibacterial agents, with a focus on long chain saturated fatty acids. Additionally, it highlights the different ways to improve their water solubility, which may be a crucial factor in increasing their antibacterial efficacy. We finish with a discussion on the challenges, strategies and opportunities for the formulation of LCFAs as antibacterial agents.
Subject(s)
Anti-Bacterial Agents , Anti-Infective Agents , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Fatty Acids/pharmacology , Fatty Acids/chemistry , Chemical Phenomena , Anti-Infective Agents/pharmacology , Bacteria , Water/chemistryABSTRACT
HYPOTHESIS: Poly(2-alkyl/aryl-oxazoline)s (PAOx) have seen a resurgence of interest in the new millennium due to their biocompatibility, low toxicity, and higher tunability compared to poly(ethylene glycol)s (PEG)s. Due to the straightforward access to hydrophilic and hydrophobic PAOx, it was hypothesized that amphiphilic PAOx should be capable of stabilizing oil/water (O/W) interfaces. Furthermore, the control of their composition, chain length, and monomer distribution could suggest the formulation of tunable emulsions. Special emphasis was given to evaluate whether spontaneously formed amphiphilic gradient copolymer could stabilize O/W emulsions. EXPERIMENTS: We prepared a series of amphiphilic block and gradient copolymers based on 2-methyl-2-oxazoline and 2-phenyl-2-oxazoline with variable hydrophilic/lipophilic balance, degree of polymerization, and monomer distribution as basis to explore their ability to stabilize emulsions. Systematic granulometry, stability, and rheology studies were performed to characterize the final emulsions. FINDINGS: Remarkably, stable O/W emulsions are obtained with only 0.5 wt% of copolymers. The finer emulsions stabilized by the most hydrophilic copoly(2-oxazoline)s allow an adjustment of their texture, as well as the concentration increase and oil content. Importantly, emulsion properties prepared with gradient copolymers show similar behavior compared with their block counterparts offering easy access to new biocompatible emulsifiers as these gradient copolymers are spontaneously formed by statistical copolymerization.
Subject(s)
Emulsifying Agents , Oxazoles , Emulsions , PolymersABSTRACT
In response to the COVID-19 and monkeypox outbreaks, we present the development of a universal disinfectant to avoid the spread of infectious viral diseases through contact with contaminated surfaces. The sanitizer, based on didecyldimethylammonium chloride (DDAC), N,N-bis(3-aminopropyl)dodecylamine (APDA) and γ-cyclodextrin (γ-CD), shows synergistic effects against non-enveloped viruses (poliovirus type 1 and murine norovirus) according to the EN 14476 standard (≥99.99% reduction of virus titer). When a disinfectant product is effective against them, it can be considered that it will be effective against all types of viruses, including enveloped viruses. Consequently, "general virucidal activity" can be claimed. Moreover, we have extended this synergistic action to bacteria (P. aeruginosa, EN 13727). Based on physicochemical investigations, we have proposed two independent mechanisms of action against bacteria and non-enveloped viruses, operating at sub- and super-micellar concentrations, respectively. This synergistic mixture could then be highly helpful as a universal disinfectant to avoid the spread of infectious viral or bacterial diseases in community settings, including COVID-19 and monkeypox (caused by enveloped viruses).
ABSTRACT
The hydrophobicity of oils is a key parameter to design surfactant/oil/water (SOW) macro-, micro-, or nano-dispersed systems with the desired features. This essential physicochemical characteristic is quantitatively expressed by the equivalent alkane carbon number (EACN) whose experimental determination is tedious since it requires knowledge of the phase behavior of the SOW systems at different temperatures and for different surfactant concentrations. In this work, two mathematical models are proposed for the rapid prediction of the EACN of oils. They have been designed using artificial intelligence (machine-learning) methods, namely, neural networks (NN) and graph machines (GM). While the GM model is implemented from the SMILES codes of a 111-molecule training set of known EACN values, the NN model is fed with some σ-moment descriptors computed with the COSMOtherm software for the 111-molecule set. In a preliminary step, the leave-one-out algorithm is used to select, given the available data, the appropriate complexity of the two models. A comparison of the EACNs of liquids of a fresh set of 10 complex cosmetic and perfumery molecules shows that the two approaches provide comparable results in terms of accuracy and reliability. Finally, the NN and GM models are applied to nine series of homologous compounds, for which the GM model results are in better agreement with the experimental EACN trends than the NN model predictions. The results obtained by the GMs and by the NN based on σ-moments can be duplicated with the demonstration tool available for download as detailed in the Supporting Information.
ABSTRACT
HYPOTHESIS: According to the so-called colloidal tectonic concept, we assumed that a single self-complementary polymer-based tecton could be used to design self-assembled emulsions. The polymer must be of high-molecular weight with balanced bipolar properties generating those of rigidity and flexibility. Linear polyethyleneimine (LPEI, 25 kDa) was used because it acts as a buffer by continuous protonation/deprotonation of the amine groups. EXPERIMENTS: The relationships between the physicochemical properties of LPEI (protonation, charge, size, aggregation and gelation) and emulsions (type, droplet size, rheological behavior and stability) were investigated to highlight the self-assembly and stabilization mechanisms during the construction events as well as the inherent properties of emulsions (responsiveness to external stimuli). FINDINGS: In aqueous solution, after a first heat and cool cycle, the adequate and spontaneous self-assembly of hydrophobic and hydrophilic sections leads to hydrogels by the formation of a 3D network where the crystallized hydrophobic domains act as knots. In the presence of various oils, the hydrogels provide long-term stable Pickering emulgels. The as-prepared emulsions are highly controllable due to their self-assembled nature (up to 10 consecutive runs). Consequently, this new approach provides a facile route to construct self-assembled, reversible and dynamics Pickering-like emulsions by simplifying the colloidal tectonics concept.
Subject(s)
Hydrogels , Polyethyleneimine , Amines , Emulsions/chemistry , Hydrogen-Ion Concentration , Oils , TemperatureABSTRACT
Emollient oils are ubiquitous ingredients of personal care products, especially skin care and hair care formulations. They offer excellent spreading properties and give end-use products a soft, pleasant and non-sticky after-feel. Emollients belong to various petro- or bio-based chemical families among which silicone oils, hydrocarbons and esters are the most prominent. Silicones have exceptional physicochemical and sensory properties but their high chemical stability results in very low biodegradability and a high bioaccumulation potential. Nowadays, consumers are increasingly responsive to environmental issues and demand more environmentally friendly products. This awareness strongly encourages cosmetics industries to develop bio-based alternatives to silicone oils. Finding effective silicon-free emollients requires understanding the molecular origin of emollience. This review details the relationships between the molecular structures of emollients and their physicochemical properties as well as the resulting functional performances in order to facilitate the design of alternative oils with suitable physicochemical and sensory properties. The molecular profile of an ideal emollient in terms of chemical function (alkane, ether, ester, carbonate, alcohol), optimal number of carbons and branching is established to obtain an odourless oil with good spreading on the skin. Since none of the carbon-based emollients alone can imitate the non-sticky and dry feel of silicone oils, it is judicious to blend alkanes and esters to significantly improve both the sensory properties and the solubilizing properties of the synergistic mixture towards polar ingredients (sun filters, antioxidants, fragrances). Finally, it is shown how modelling tools (QSPR, COSMO-RS and neural networks) can predict in silico the key properties of hundreds of virtual candidate molecules in order to synthesize only the most promising whose predicted properties are close to the specifications.
Subject(s)
Cosmetics , Emollients , Cosmetics/chemistry , Emollients/chemistry , Esters/chemistry , Humans , Oils , Physical Functional Performance , Silicone Oils , Silicones/chemistryABSTRACT
Amphiphilic gradient copolymers represent a promising alternative to extensively used block copolymers due to their facile one-step synthesis by statistical copolymerization of monomers of different reactivity. Herein, an in-depth analysis is provided of micelles based on amphiphilic gradient poly(2-oxazoline)s with different chain lengths to evaluate their potential for micellar drug delivery systems and compare them to the analogous diblock copolymer micelles. Size, morphology, and stability of self-assembled nanoparticles, loading of hydrophobic drug curcumin, as well as cytotoxicities of the prepared nanoformulations are examined using copoly(2-oxazoline)s with varying chain lengths and comonomer ratios. In addition to several interesting differences between the two copolymer architecture classes, such as more compact self-assembled structures with faster exchange dynamics for the gradient copolymers, it is concluded that gradient copolymers provide stable curcumin nanoformulations with comparable drug loadings to block copolymer systems and benefit from more straightforward copolymer synthesis. The study demonstrates the potential of amphiphilic gradient copolymers as a versatile platform for the synthesis of new polymer therapeutics.
Subject(s)
Curcumin , Micelles , Curcumin/chemistry , Drug Carriers/chemistry , Hydrophobic and Hydrophilic Interactions , Polymers/chemistryABSTRACT
Pickering emulsions, foams, bubbles, and marbles are dispersions of two immiscible liquids or of a liquid and a gas stabilized by surface-active colloidal particles. These systems can be used for engineering liquid-liquid-solid and gas-liquid-solid microreactors for multiphase reactions. They constitute original platforms for reengineering multiphase reactors towards a higher degree of sustainability. This Review provides a systematic overview on the recent progress of liquid-liquid and gas-liquid dispersions stabilized by solid particles as microreactors for engineering eco-efficient reactions, with emphasis on biobased reagents. Physicochemical driving parameters, challenges, and strategies to (de)stabilize dispersions for product recovery/catalyst recycling are discussed. Advanced concepts such as cascade and continuous flow reactions, compartmentalization of incompatible reagents, and multiscale computational methods for accelerating particle discovery are also addressed.
ABSTRACT
This work reports a novel and visual method for the simultaneous determination of the chemical (kr ) and the physical (kq ) quenching rate constants of singlet oxygen (1 O2 ,1 ∆g ) in aqueous media. It is based on the disruption, by a water-soluble substrate S, of the 1 O2 chemiluminescence (CL) generated by the H2 O2 /Na2 MoO4 catalytic system. A mathematical analysis of the CL signal at 1270 nm vs time provides separately the overall (kr + kq ) and the chemical (kr ) quenching rate constants. In ordinary water (H2 O), 1 O2 lifetime is short and the CL intensity is weak allowing solely the investigation of very reactive substrates for which (kr + kq ) > 3 × 106 m-1 s-1 while, in D2 O, 1 O2 lifetime is significantly longer lifetime and the CL signal is much stronger allowing the study of poorly reactive substrates for which (kr + kq ) > 4 × 105 m-1 s-1 . The method has been successfully tested on a series of anionic and nonionic water-soluble naphthalene derivatives commonly used as bio-compatible 1 O2 carriers. The obtained kr and kq values are in good agreement with the values determined by conventional techniques, namely, flash photolysis and competitive kinetics with a reference quencher.
Subject(s)
Luminescence , Singlet Oxygen , Antioxidants , Kinetics , Oxygen , WaterABSTRACT
We present the development of surfactant-free, silica-free and fully biobased oil-in-water antimicrobial Pickering emulsions, based on the self-assembly of ß-cyclodextrin and phytoantimicrobial oils (terpinen-4-ol or carvacrol). Undecylenic acid (UA), derived from castor oil, can be used as bio-based drug to treat fungal infection, but is less effective than petroleum-based drugs as azole derivatives. To maximize its antifungal potential, we have incorporated UA in fully biobased Pickering emulsions. These emulsions are effective against fungi, Gram-positive and Gram-negative bacteria. The carvacrol emulsion charged with UA is +390 % and +165 % more potent against methicillin-resistant S. aureus (MRSA), compared to UA and azole-based commercial formulations. Moreover, this emulsion is up to +480 % more efficient that UA ointment against C. albicans. Finally, remarkable eradication of E. coli and MRSA biofilms was obtained with this environmental-friendly emulsion.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Cymenes/pharmacology , Undecylenic Acids/pharmacology , beta-Cyclodextrins/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Candida albicans/drug effects , Castor Oil/chemistry , Cymenes/chemical synthesis , Cymenes/chemistry , Dose-Response Relationship, Drug , Emulsions/chemical synthesis , Emulsions/chemistry , Emulsions/pharmacology , Escherichia coli/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship , Undecylenic Acids/chemical synthesis , Undecylenic Acids/chemistry , beta-Cyclodextrins/chemical synthesis , beta-Cyclodextrins/chemistryABSTRACT
In response to the current pandemic situation, we present the development of an effective virucidal and biocidal solution to prevent from the spread of infectious diseases through contact with contaminated surfaces. The disinfectants, based on equimolar mixtures of didecyldimethylammonium chloride ([DiC10][Cl]), dodecyloctaglycol (C12E8), and cyclodextrin (CD), show synergistic effects against enveloped viruses (RSV, HSV-1, VACV) and fungi (C. albicans), and additive responses against bacteria (P. aeruginosa). These synergistic mixtures could then be highly helpful for prevention of respiratory illnesses, since a boosted activity allows: (i) a faster eradication of pathogens, (ii) a shorter contact time, and (iii) a complete and broad-spectrum eradication to avoid spread of resistant strains (including bacteria and fungi).
Subject(s)
Cyclodextrins , Disinfectants , Viruses , Bacteria , Disinfectants/pharmacology , DisinfectionABSTRACT
The viscosities of pure liquids are estimated at 25 °C, from their molecular structures, using three modeling approaches: group contributions, COSMO-RS σ-moment-based neural networks, and graph machines. The last two are machine-learning methods, whereby models are designed and trained from a database of viscosities of 300 molecules at 25 °C. Group contributions and graph machines make use of the 2D-structures only (the SMILES codes of the molecules), while neural networks estimations are based on a set of five descriptors: COSMO-RS σ-moments. For the first time, leave-one-out is used for graph machine selection, and it is shown that it can be replaced with the much faster virtual leave-one-out algorithm. The database covers a wide diversity of chemical structures, namely, alkanes, ethers, esters, ketones, carbonates, acids, alcohols, silanes, and siloxanes, as well as different chemical backbone, i.e., straight, branched, or cyclic chains. A comparison of the viscosities of liquids of an independent set of 22 cosmetic oils shows that the graph machine approach provides the most accurate results given the available data. The results obtained by the neural network based on sigma-moments and by the graph machines can be duplicated easily by using a demonstration tool based on the Docker technology, available for download as explained in the Supporting Information. This demonstration also allows the reader to predict, at 25 °C, the viscosity of any liquid of moderate molecular size (M < 600 Da) that contains C, H, O, or Si atoms, starting either from its SMILES code or from its σ-moments computed with the COSMOtherm software.
Subject(s)
Cosmetics , Machine Learning , Neural Networks, Computer , Oils , ViscosityABSTRACT
We present self-assembled Pickering emulsions containing biocidal phytochemical oils (carvacrol and terpinen-4-ol) and ß-cyclodextrin able to potentiate the antimicrobial and antibiofilm activity of miconazoctylium bromide. The carvacrol-containing emulsion is 2-fold more sensitive against C. albicans and S. aureus and highly active against E. coli, compared to the commercial cream containing miconazole nitrate. Moreover, this emulsion shows a synergistic effect against fungi, additive responses against bacteria, and remarkable staphylococcal biofilm eradication. These results are associated with membrane permeabilization, enzymes inhibition, and the accumulation of reactive oxygen species in microorganisms.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Biofilms/drug effects , Cyclodextrins/chemistry , Emulsions/chemistry , Candida albicans/drug effects , Cymenes/pharmacology , Escherichia coli/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/physiology , Terpenes/pharmacologyABSTRACT
Alumina-functionalized ordered mesoporous silica SBA-15 particles have been proposed to stabilize Pickering emulsions. Functionalization of SBA-15 particles have been performed by depositing alumina using a two-step synthesis (first, silica condensation, followed by alumina precipitation). Three different Al to Si ratios have been prepared. The calcined materials have been characterized by TEM, SEM, XRD, N2 physisorption, and zeta potential, in order to determine key physicochemical properties, and the alumina localization. The emulsifying and stabilizing properties of the calcined particles have been evaluated for water/toluene-based Pickering emulsions.
ABSTRACT
The standard HLD (Hydrophilic-Lipophilic-Deviation) equation expressing quantitatively the deviation from the "optimum formulation" of Surfactant/Oil/Water systems is normalized and simplified into a relation including only the three more meaningful formulation variables, namely (i) the "Preferred Alkane Carbon Number" PACN which expresses the amphiphilicity of the surfactant, (ii) the "Equivalent Alkane Carbon Number" EACN which accurately reflects the hydrophobicity of the oil and (iii) the temperature which has a strong influence on ethoxylated surfactants and is thus selected as an effective, continuous and reversible scanning variable. The PACN and EACN values, as well as the "temperature-sensitivity-coefficient"τ of surfactants are determined by reviewing available data in the literature for 17 nonionic n-alkyl polyglycol ether (CiEj) surfactants and 125 well-defined oils. The key information used is the so-called "fish-tail-temperature" T* which is a unique data point in true ternary CiEj/Oil/Water fish diagrams. The PACNs of CiEj surfactants are compared with other descriptors of their amphiphilicity, namely, the cloud point, the HLB number and the PIT-slope value. The EACNs of oils are rationalized by the Effective-Packing-Parameter concept and modelled thanks to the COSMO-RS theory.
ABSTRACT
Supramolecular preorganization and interfacial recognition can provide useful architectures for colloidal building. To this aim, a novel approach, based on colloidal tectonics involving two surface-active particles containing both recognition and catalytic sites, has been developed for controlling the formation and the properties of Pickering emulsions. This was illustrated by the combination of dodecyltrimethylammonium phosphotungstate nanoparticles, [C12]3[PW12O40], and silica particles functionalized with alkyl and sulfonic acid groups, [C n /SO3H]@SiO2. The interfacial self-assembly occurs by the penetration of the alkyl chains of [C n /SO3H]@SiO2 into the [C12]3[PW12O40] supramolecular porous structure constituted of polar and apolar regions. The emulsions were used as a non-nitric acid route for adipic acid synthesis from the one-pot oxidative cleavage of cyclohexene oxide with aqueous H2O2. The catalytic performance was significantly boosted due to the synergistic interactions between the particles.
ABSTRACT
The human nail, like any biological material, is not readily available in large amounts and shows some variability from one individual to another. Replacing it by synthetic models is of great interest to perform reproducible and reliable tests in order to assess drug diffusion or nail lacquer adhesion for example. Keratin films, produced at the lab scale from natural hair, and the commercially available Vitro-nail® sheets have been proposed as models of human nails. In this study, we have investigated in detail these two materials. Surface aspect, composition, surface energy and water permeation were determined by SEM-EDS, ATR-FTIR, XPS, DVS and tensiometry and were compared to those of nails clippings. The development of a probe tack test using a rotational rheometer allowed us to measure the adhesion of three different nail lacquers on each substrate and the results were correlated with the surface state. It is shown that except roughness, keratin films exhibit similar composition, water sorption and surface energy as human nails. Vitro-nail® presents a more hydrophilic and permeable behavior than natural nail due to probable higher proportions of amide functions and absence of disulfide bridges. With the aim to improve nail lacquer residence, the importance of adsorption, electrostatic and mechanical adhesions as well as water sorption behavior is highlighted and allowed to show the importance of roughness, a low surface energy, a moderate hydrophobicity and an ability to form hydrogen and electrostatic bonds in order to optimize adhesion.
Subject(s)
Models, Biological , Nails/chemistry , Adhesiveness , Adsorption , Cellulose/analogs & derivatives , Cellulose/chemistry , Humans , Keratins/chemistry , Plasticizers/chemistry , Static Electricity , Water/chemistryABSTRACT
Supramolecular hybrid functional nanoparticles (NPs) can be obtained via the colloidal tectonics approach provided that multiple interactive molecular tectons are used. Herein, the programmable synthesis of novel hybrid core-shell nanoparticles via the following sequential steps is reported: (i)â complexation of 1-decanol by the ß-cyclodextrin (ß-CD), (ii)â spontaneous self-assembly into CD NPs, (iii)â adsorption of polyoxometalate anions, PW12 O40 3- , on the polar neutral interface of the CD NPs. Such an approach paves the way for the design of novel and original materials and systems.
ABSTRACT
HYPOTHESIS: In contrast to anionic and nonionic amphiphilic substances, bio-based cationic ones are very rare. Cationic amphiphiles are mostly based on quaternary ammonium, pyridinium or imidazolium groups that are either badly biodegradable or have toxic residues even after degradation. In the search for green alternatives to cationic hydrotropes and amphiphiles, natural l-carnitine could be a promising candidate for a cationic headgroup. EXPERIMENTS: By esterification of carnitine in one step and with low cost, cationic molecules with alkyl chain length of n=2-14 could be obtained. Their thermal properties, aggregation behaviour and cytotoxicity were determined. Hydrophobic compounds were solubilized in their aqueous solutions and the PIT-slope method was applied to determine a relative hydrophilicity. FINDINGS: It was found that some pure carnitine ester bromides were liquid at room temperature and thus can be classified as ionic liquids. They are highly water-soluble, and in aqueous solutions, they showed hydrotrope or surfactant behaviour depending on their alkyl chain length. Their high hydrotropic efficiency was demonstrated by solubilizing Disperse Red 13, while also biomolecules, like vanillin, could be dissolved in reasonable amounts. In all tests, they performed at least as good as the tested reference substances, while showing similar cytotoxicity towards human skin keratinocytes, thus demonstrating their potential as green functional amphiphilic molecules of positive charge.