Kushnazarova, Rushana Abdurashitovna

Kushnazarova R., Mirgorodskaya A., Bushmeleva K., Vyshtakalyuk A., Lenina O., Petrov K., Zakharova L.

Kushnazarova R., Mirgorodskaya A., Bekrenev D., Kuznetsov D., Lyubina A., Voloshina A., Zakharova L.

New hexadecylpiperidinium surfactants, containing one or two butylcarbamate fragments, were synthesized. The antimicrobial activity, toxicity, aggregation behavior in aqueous solutions, and solubilization capacity of these surfactants towards the hydrophobic drug ibuprofen were characterized. These surfactants demonstrated a high antimicrobial activity against a wide range of pathogenic bacteria, including both Gram-positive and Gram-negative strains, as well as fungi. By forming mixed-micellar compositions of the cationic surfactant 1-CB(Bu)-P-16 and the nonionic surfactant Brij®35, highly functional and low-toxic formulations were obtained. Furthermore, the transition from mixed micelles to niosomes was accomplished, enhancing their potential as drug delivery systems. Niosomes were found to be less toxic compared to mixed micelles, while also increasing the solubility of ibuprofen in water. The modification of niosomes with cationic surfactants made it possible to increase the stability of the system and improve the solubility of the drug. The data obtained indicate that these new carbamate-containing hexadecylpiperidinium surfactants have significant potential in biomedical applications, particularly in the formulation of advanced drug delivery systems.

Kushnazarova R.A., Mirgorodskaya A.B., Vasilieva E.A., Lenina O.А., Petrov K.A., Zakharova L.Y.

AbstractBACKGROUNDSurfactants, particularly non‐ionic ones, are widely used as adjuvants in pesticide formulations due to their ability to maintain pesticide effectiveness without changing solution properties, such as pH. While non‐ionic surfactants are generally low‐toxic, stable, and excellent dispersants with high solubilization capabilities, they may be less effective than cationic surfactants, which offer superior surface activity, transport properties, and antimicrobial action. This study investigates the efficacy of new piperidinium surfactants with carbamate fragments as adjuvants in insecticide formulations containing imidacloprid. The efficacy of these formulations is being assessed against greenhouse whitefly, a pest known to harm cultivated and ornamental flowering plants.RESULTSThe aggregation behavior of piperidinium surfactants containing carbamate fragments was investigated, and their wetting effect was evaluated. Synthesized surfactants have lower CMC values compared to their methylpiperidinium analogue. The effect of piperidinium surfactants on the insecticide concentration on the surface and inside tomato leaves was assessed using spectrophotometric methods. It was found that the introduction of piperidinium surfactants with carbamate fragment at a concentration of 0.1% wt. allows for decrease in lethal concentration of imidacloprid up to 10 times, thereby testifying the marked increase in the effectiveness of imidacloprid against the greenhouse whitefly insect pest (Trialeurodes vaporariorum). It was shown that the main factors responsible for the enhanced efficacy of the insecticide were the ability of the surfactant to increase the concentration of imidacloprid on the leaf surfaces and improve their penetration into the plant.CONCLUSIONThe presented work employed a comprehensive approach, which significantly increases the generalizability of the results obtained and provides the ability to predict the effect and target selection of adjuvants. © 2024 Society of Chemical Industry.

Kushnazarova R.A., Mirgorodskaya A.B., Bekrenev D.D., Lyubina A.P., Lenina O.A., Petrov K.A., Voloshina A.D., Zakharova L.Y.

The aggregation behavior of mixed micellar solutions based on 2-hydroxyethylpiperidinium surfactants and nonionic surfactant Brij® 35 was investigated. The critical micelle concentrations determined by varying the component ratio suggest a negative deviation from the ideal mixing model (synergistic effect). It was demonstrated that the magnitude of the deviation from ideal mixing behavior depends on the alkyl chain length in the cationic surfactant and on the component ratio. The solubilization effect of the binary systems on hydrophobic substances was evaluated taking Orange OT dye and ibuprofen drug as examples. It was found that the piperidinium surfactants studied, both individually and in compositions containing up to 50% of the nonionic surfactant, exhibit high antimicrobial activity comparable to that of commercial antibiotics.

Kushnazarova R.A., Mirgorodskaya A.B., Kuznetsov D.M., Vasilieva E.A., Amerhanova S.K., Voloshina A.D., Zakharova L.Y.

The biomimetic nature of supramolecular systems, the structural similarity of synthetic surfactants to biomolecules (lipids, proteins), provide them with high membranotropy, the ability to overcome biological barriers, and affinity towards biosubstances. Despite rather high toxicity cationic surfactants are of importance as antimicrobial agents, gene nanocarriers and mitochondria targeted ligands. To minimize this limitation, cationic amphiphilic matrix undergoes modification with various functional groups. In this work, new piperidinium cationic surfactants containing one or two carbamate fragments were prepared; their aggregation behavior was systematically studied by tensiometery, spectrophotometry and fluorimetry. The presence of a carbamate fragment leads to a 2–3-fold decrease in critical micelle concentration and to a significant increase in solubilization capacity compared to unsubstituted analogue. Evaluation of the antimicrobial effect showed that all compounds exhibit high bactericidal and fungicidal activity against a wide range of pathogenic microorganisms, including their resistant forms. Importantly, the introducing carbamate moiety allows of decreasing hemolytic activity of cationic surfactants. The data obtained make it possible to recommend carbamate piperidinium surfactants as effective biocompatible and biodegradable nanocontainers for hydrophobic probes with high antimicrobial effect and moderate hemolytic activity.

Zhiltsova E.P., Valeeva F.G., Kuznetsov D.M., Kushnazarova R.A., Vasilieva E.A., Mirgorodskaya A.B., Zakharova L.Y.

The hydrolytic decomposition of the organophosphorus ecotoxicant paraoxon in alkaline micellar solutions of a cationic surfactant with a carbamate fragment (CB-2-16) has been investigated by means of spectrophotometry. The stronger catalytic effect of micellar solutions aged during several days in comparison with freshly prepared ones has been associated with alkaline hydrolysis of the carbamate surfactant and the formation of a mixed system of CB-2-16 with its decomposition product cetyl(2-hydroxyethyl)dimethylammonium bromide (1H NMR spectroscopy data). In the absence of alkali, the decomposition products of the carbamate surfactant have not been detected for more than four months, indicating its hydrolytic stability in a neutral environment.

Mirgorodskaya A.B., Kushnazarova R.A., Voloshina A.D., Amerhanova S.K., Lenina O.A., Petrov K.A., Ya. Zakharova L.

The aggregation behavior of mixed micellar solutions based on cationic hexadecylpiperidinium surfactants containing one or two hydroxy substituents and nonionic surfactant Tween 80 have been investigated by tensiometric, fluorimetric, and dynamic light scattering methods. The values of the critical micelle concentration were determined at varying component ratio. Based on the data obtained and their analysis using the Clint’s and Rubingh’s models one can conclude about a negative deviation from the ideal mixing (synergistic effect). It has been found out that the piperidinium surfactants, both in individually form and in mixed compositions with 0.5 molar fraction of nonionic surfactant showed high antimicrobial activity comparable to that of commercial antibiotics, while the presence of Tween 80 significantly reduced the acute toxicity of the system. A study of the membranotropic properties of piperidinium surfactants and the mixed systems, as well as an analysis of their effect on the permeability of the cell wall and cytoplasmic membrane of Staphylococcus aureus suggested that the antimicrobial effect was not associated with the destruction of the cell membrane, but was due to specific interactions of surfactants with cell components.

Mirgorodskaya A.B., Kushnazarova R.A., Zakharova L.Y., Ulyanova A.A., Litvinov D.Y., Blinkov A.O., Divashuk M.G., Kochanova I.A., Nesterova L.M.

Surfactants are often added to herbicidal formulations to improve the delivery of the herbicide into plants. In this study a new herbicidal formulation was formed based on the clopyralid with 0.01% gemini surfactant hexanediyl-1,6-bis(dimethylcetylammonium bromide) (16-6-16) as an adjuvant. The increase in the efficiency of the formulation was associated with the formation of a supramolecular surfactant–herbicide complex (SMC), which has improved wetting properties, provides high clopyralid concentration on the leaf surface, and has higher penetrating ability compared to surfactant-free clopyralid solutions. Comparison of the herbicidal action of clopyralid–16-6-16 SMC with two commercial formulations of the same concentration of clopyralid was performed using digital phenotyping of the model weed plant cocklebur (Xanthium strumarium). Based on the spectral indices NDVI (normalized differential vegetation index) and PSRI (plant senescence reflectance index) and key morphological indexes of the leaf angle, plant height, and leaf area, we showed that clopyralid formulations strongly affected the plants and that the strongest and most durable effect was exerted by the clopyralid–16-6-16 SMC formulation.

Mirgorodskaya A.B., Kushnazarova R.A., Lenina O.A., Petrov K.A., Zakharova L.Y.

Abstract A series of microemulsions based on oleic acid and Tween 80, modified with piperidinium surfactants, have been obtained and characterized. The effect of additives on the size, stability, and solubilization effect of the formed systems with respect to hydrophilic (rhodamine B) and hydrophobic (indomethacin) substances have been investigated. Varying of the components ratio has allowed preparation of the microemulsions with strongly different viscosity: from easy-flowing formulations to gels. Kinetic parameters describing release of the substrates from the microemulsions have been obtained. In vivo tests of the anti-inflammatory action of the microemulsions loaded with indomethacin have shown that the presence of piperidinium surfactants enhances the therapeutic effect of the drug.

Mirgorodskaya A., Kushnazarova R., Pavlov R., Valeeva F., Lenina O., Bushmeleva K., Kuryashov D., Vyshtakalyuk A., Gaynanova G., Petrov K., Zakharova L.

Abietic acid, a naturally occurring fir resin compound, that exhibits anti-inflammatory and wound-healing properties, was formulated into biocompatible emulgels based on stable microemulsions with the addition of a carbamate-containing surfactant and Carbopol® 940 gel. Various microemulsion and emulgel formulations were tested for antioxidant and wound-healing properties. The chemiluminescence method has shown that all compositions containing abietic acid have a high antioxidant activity. Using Strat-M® skin-modelling membrane, it was found out that emulgels significantly prolong the release of abietic acid. On Wistar rats, it was shown that microemulsions and emulgels containing 0.5% wt. of abietic acid promote the rapid healing of an incised wound and twofold tissue reinforcement compared to the untreated group, as documented by tensiometric wound suture-rupture assay. The high healing-efficiency is associated with a combination of antibacterial activity of the formulation components and the anti-inflammatory action of abietic acid.

Mirgorodskaya A.B., Tyryshkina A.A., Kushnazarova R.A., Kuznetsov D.M., Zakharova L.Y.

Data characterizing the effect of electrolyte additives (sodium chloride and salicylate, polyacrylic acid) on the critical micelle concentration and the size of hexadecylpiperidinium surfactant aggregates, including those containing one or two hydroxyl groups, were obtained by tensiometry and dynamic light scattering methods. The solubilization effect of surfactant—electrolyte systems with respect to the hydrophobic dye probe Orange OT was evaluated. The conditions (pH, ratio of components) for the formation of soluble (nonstoichiometric) and insoluble (stoichiometric) polymer-colloidal complexes were determined for a surfactant—polyacrylic acid system.

Mirgorodskaya A.B., Kushnazarova R.A., Sharonova N.L., Rakhmaeva A.M., Tyryshkina A.A., Kuznetsov D.M., Nikitin E.N., Zakharova L.Y.

New piperidinium surfactants with a benzyl fragment in the head group were synthesized and characterized. The critical micelle concentrations, degrees of binding of counterions, and aggregation numbers were determined for aqueous solutions of these surfactants by tensiometry, conductometry, and spectrophotometry. The wetting action of the synthesized surfactants was characterized, and their solubilization capacity with respect to the hydrophobic dye Orange OT and fungicide carbendazim was estimated. Antimicrobial activity of the surfactants to a number of plant pathogenic strains was revealed, which is especially pronounced with respect to gram-positive bacteria Clavibacter michiganensis, Curtobacterium flaccumfaciens, and Rathayibacter iranicus (minimum bactericidal concentration 0.5–4 µg mL−1).

Kushnazarova R.A., Mirgorodskaya A.B., Voloshina A.D., Lyubina A.P., Kuznetsov D.M., Lenina O.A., Zakharova L.Y.

Mirgorodskaya A.B., Kushnazarova R.A., Kuznetsov D.M., Tyryshkina A.A., Zakharova L.Y.

The aggregation behavior of new cationic hexadecyl surfactants with one or two alkylcarbamate fragments in the head group in water was studied using conductometry, spectrophotometry, fluorescence spectroscopy, and dynamic light scattering, and their catalytic action in hydrolytic processes was examined. Kinetic parameters of the alkaline hydrolysis of carboxylic acid esters (p-nitrophenyl acetate and p-nitrophenyl caprinate) were obtained upon the variation of the structures of surfactant head groups and the pH of solution. It was shown that the catalytic effect of micelle-forming surfactants with a single carbamate fragment is higher than that of the corresponding dicarbamate compounds, and it decreases with the alkyl chain length of substituents in head groups. It was found that carbamate surfactants capable of vesicle formation accelerate the hydrolysis of the test esters to a greater extent than their analogs forming micelles: the observed acceleration of the process can exceed two orders of magnitude in the case of a compound with the decyl substituent in a carbamate fragment.

Kushnazarova R.A., Mirgorodskaya A.B., Mikhailov V.A., Belousova I.A., Zubareva T.M., Prokop’eva T.M., Voloshina A.D., Amerhanova S.K., Zakharova L.Y.

Dicationic imidazolium surfactants of the 1,1′-(2-hydroxypropan-1,3-diyl)bis(3-alkyl-1H-imidazol-3-ylium)chloride series with a variable hydrophobic chain length have been synthesized and characterized. The values of their critical micelle concentration have been determined by tensiometry, conductometry and spectrophotometry. Significant antimicrobial activity of these surfactants against a number of pathogenic bacteria and fungi was revealed. It was found that decyl and dodecyl derivatives turned out to be leader compounds, which surpassed reference antibiotics in their action and showed activity against resistant strains. The kinetic parameters reflecting the high catalytic effect of the tested dicationic imidazolium surfactants in the alkaline hydrolysis of 4-nitrophenyl esters of phosphonic, phosphoric, and toluenesulfonic acids have been obtained.

Kuznetsova D.A., Kuznetsov D.M., Valeeva F.G., Lyubina A.P., Voloshina A.D., Zakharova L.Y.

Vasilieva E.A., Babkin R.A., Valeeva F.G., Kuznetsov D.M., Nizameev I.R., Lyubina A.P., Voloshina A.D., Zakharova L.Y.

Deeplaxmi Dasharath Kambli, Cleona Elizabeth Mary DCruz, Kumar L., Shirodkar R.K.

Felodipine, a Dihydropyridine calcium channel antagonist, is widely used to treat hypertension and angina pectoris. Its highly lipophilic nature and low aqueous solubility classify it as a Biopharmaceutics Classification System Class II Drug. When administered orally, Felodipine undergoes extensive first-pass hepatic metabolism, resulting in low oral bioavailability (15%) and posing challenges for effective antihypertensive therapy. This study aimed to formulate drug-loaded nanovesicular Spanlastics within oral fast-dissolving films, enabling buccal mucosa delivery to bypass hepatic metabolism and enhance drug bioavailability. Felodipine nanovesicular Spanlastics were formulated using a modified Ethanol Injection method. Design Expert® Software Version 13 and a 23 factorial design model determined the effect of formulation variables on response variables. The Spanlastics, characterized for particle size (ranging from 155.7 to 308.9 nm) and entrapment efficiencies (84.68 to 88.36%), showed lamellar, circularly shaped vesicles as observed through Optical and Transmission Electron Microscopy. These optimized Spanlastics were incorporated into oral fast-dissolving films, which exhibited substantial flexibility, sufficient mechanical strength, a disintegration time of 35 s, and rapid drug release of 95.99% within 5 min. Scanning Electron Microscopy imaging confirmed a smooth, porous, and uniform surface of the films. Short-term stability studies indicated that the films maintained stable physical and structural attributes. This research confirmed that Felodipine Spanlastic vesicles, due to their nanosize, enhance mucosal permeation and act as effective nanocarriers. Their incorporation into fast-dissolving oral films improves bioavailability through oro-mucosal tissue absorption for buccal delivery.

Putra B.R., Nurwidayanti E., Fadilah S., Khalil M., Rustami E., Wahyuni W.T.

In this study, we developed electrochemical sensors based on the composite of hydroxylated multiwalled carbon nanotubes (MWCNT-OH) and graphene for paraoxon-ethyl detection as pesticide residues in agricultural products. Chemical treatment was employed to produce MWCNT-OH from pristine MWCNT and its composite with graphene was subsequently characterized using FTIR, Raman spectroscopy, FESEM-EDX, TEM, and XPS techniques. The MWCNT-OH/graphene composite was employed as an electrode modifier on the glassy carbon electrode (GCE) surface, and its electroanalytical performances were studied using differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) techniques. It was revealed the optimum composition ratio between MWCNT-OH and graphene was 2:8, for paraoxon-ethyl detection at pH 7. This could be attributed to the enhanced electrocatalytic activity in the MWCNT-OH/graphene composite which displayed a linear range of paraoxon-ethyl concentration as 0.1–100 µM with a lower detection limit of 10 nM and a good sensitivity of 1.60 µA µM cm−2. In addition, the proposed sensor shows good reproducibility, stability, and selectivity in the presence of 10 different interfering compounds including other pesticides. Ultimately, this proposed sensor was tested to determine the paraoxon-ethyl concentrations in green apples and cabbage as samples of agricultural products. The obtained concentrations of paraoxon-ethyl from this proposed sensor show no significant difference with standard spectrophotometric techniques suggesting this sensing platform might be further developed as a rapid detection of pesticide residue in agricultural products.

Kłosowska-Chomiczewska I.E., Burakowska G., Żmuda-Trzebiatowska P., Soukup A., Rok-Czapiewska I., Hallmann E., Pokynbroda T., Karpenko O., Mędrzycka K., Macierzanka A.

A novel, cost-effective, partially purified biosurfactant in the form of a rhamnolipid biocomplex (RLBC) was investigated for its emulsifying properties. The RLBC was obtained through the cultivation of Pseudomonas sp. SP-17 on glycerol, followed by acidic precipitation, without the use of organic solvents for isolation or purification. Composed of rhamnolipids (RLs) and the exopolysaccharide alginate, RLBC exhibited emulsifying properties towards rapeseed oil comparable to those of purified RLs at concentrations as low as 0.15% (w/w), sufficient for the effective stabilisation of oil-in-water (o/w) high internal phase emulsions (HIPEs, 80% oil). Dynamic light scattering analysis revealed similar droplet sizes (9.54 ± 0.96 µm for RLBC vs. 8.93 ± 0.58 µm for RLs), while multiple light scattering confirmed high emulsion stability over 120 days. The emulsions displayed shear-thinning behaviour, with yield stresses of approximately 11.5 Pa and 7.7 Pa for systems prepared with RLBC and RLs, respectively, after seven days of pre-storage. Although increasing the RLBC concentration from 0.15% to 1% (w/w) slightly improved the degree of emulsion dispersion, it did not substantially impact the long-term stability observed at the lowest concentration. Biodegradation tests demonstrated that the RLBC preparations are environmentally friendly alternatives to synthetic surfactants, achieving 60% biodegradation within 2.5 days and complete biodegradation within 14 days, which outperformed synthetic emulsifiers. The RLBC offers both environmental and economic advantages over purified RLs, including reduced production costs and the elimination of organic solvents. Our findings highlight the potential of RLBC for stabilising HIPEs in applications requiring sustainable and biodegradable formulations, such as cosmetics, lubricants, and industrial fluids widely manufactured and utilised today.

Milutinov J., Krstonošić V., Ćirin D., Hadnađev M., Đanić M., Pavlović N.

Park J.Y., Baek D., Min H., Yeom B., Ha J.S., Kim Y.

Khan S., Do C., Ho E.A.

Ocular diseases have a major impact on patient’s vision and quality of life, with approximately 2.2 billion people have visual impairment worldwide according to the findings from the World Health Organization (WHO). The eye is a complex organ with unique morphology and physiology consisting of numerous ocular barriers which hinders the entry of exogenous substances and impedes drug absorption. This in turn has a substantial impact on effective drug delivery to treat ocular diseases, especially intraocular disorders which has consistently presented a challenge to eye care professionals. The most common method of delivering medications to the eye is topical instillation of eye drops. Although this approach is a viable option for treating many ocular diseases remains a major challenge for the effective treatment of posterior ocular conditions. Up till now, incessant efforts have been committed to design innovative drug delivery systems with the hopes of potential clinical application. Modern developments in nanocarrier’s technology present a potential chance to overcome these obstacles by enabling targeted delivery of the loaded medication to the eyes with improved solubility, delayed release, higher penetration and increased retention. This review covers the anatomy of eye with associated ocular barriers, ocular diseases and administration routes. In addition it primarily focuses on the latest progress and contemporary applications of ophthalmic formulations providing specific insight on nanostructured drug delivery carriers reported over the past 5 years highlighting their values in achieving efficient ocular drug delivery to both anterior and posterior segments. Most importantly, we outlined in this review the macro and nanotechnology based ophthalmic drug formulations that are being patented or marketed so far for treating ocular diseases. Finally, based on current trends and therapeutic concepts, we highlighted the challenges faced by novel ocular drug delivery systems and provided prospective future developments for further research in these directions. We hope that this review will serve as a source of motivation and ideas for formulation scientists in improving the design of innovative ophthalmic formulations.

Abu Koush A., Popa E.G., Pricop D.A., Nita L., Foia C., Pauna A.R., Buca B.R., Pavel L.L., Mititelu-Tartau L.

Background: Lipid vesicles, especially those utilizing biocompatible materials like chitosan (CHIT), hold significant promise for enhancing the stability and release characteristics of drugs such as indomethacin (IND), effectively overcoming the drawbacks associated with conventional drug formulations. Objectives: This study seeks to develop and characterize novel lipid vesicles composed of phosphatidylcholine and CHIT that encapsulate indomethacin (IND-ves), as well as to evaluate their in vitro hemocompatibility. Methods: The systems encapsulating IND were prepared using a molecular droplet self-assembly technique, involving the dissolution of lipids, cholesterol, and indomethacin in ethanol, followed by sonication and the gradual incorporation of a CHIT solution to form stable vesicular structures. The vesicles were characterized in terms of size, morphology, Zeta potential, and encapsulation efficiency and the profile release of drug was assessd. In vitro hemocompatibility was evaluated by measuring erythrocyte lysis and quantifying hemolysis rates. Results: The IND-ves exhibited an entrapment efficiency of 85%, with vesicles averaging 317.6 nm in size, and a Zeta potential of 24 mV, indicating good stability in suspension. In vitro release kinetics demonstrated an extended release profile of IND from the vesicles over 8 h, contrasting with the immediate release observed from plain drug solutions. The hemocompatibility assessment revealed that IND-ves exhibited minimal hemolysis, comparable to control groups, indicating good compatibility with erythrocytes. Conclusions: IND-ves provide a promising approach for modified indomethacin delivery, enhancing stability and hemocompatibility. These findings suggest their potential for effective NSAID delivery, with further in vivo studies required to explore clinical applications.

Hussain A., Altamimi M.A., Alshammari M.A.

Hasan R., Bhuia M.S., Chowdhury R., Saha S., Khan M.A., Afroz M., Ansari S.A., Ansari I.A., Melo Coutinho H.D., Islam M.T.

Peng H., Zhao M., Liu X., Tong T., Zhang W., Gong C., Chowdhury R., Wang Q.

Pirojiya H., Dudhat K.

Niosomes, formed from non-ionic surfactants, are emerging as powerful nanocarriers in drug delivery, addressing critical needs for stability, biocompatibility, and flexibility in drug encapsulation. This review investigates the development, preparation techniques, and applications of niosomes, underscoring their potential for advancing targeted, controlled, and sustained drug delivery in modern medicine. A comprehensive review of niosome-based drug delivery systems was conducted, examining key preparation methods such as thin-film hydration, reverse-phase evaporation, and sonication. Studies were analyzed for drug encapsulation efficiency, release kinetics, and formulation stability. Special focus was given to surface modifications and green synthesis approaches that enhance niosomal stability while promoting eco-friendly production. Niosomes demonstrate clear advantages over traditional drug carriers, offering improved drug stability, enhanced bioavailability, and precise targeting capabilities. Green synthesis using biodegradable surfactants was found to improve the safety and sustainability profile of niosomes, making them well-suited for modern healthcare demands. Applications in areas like cancer therapy, vaccine delivery, and chronic disease management showcase significant therapeutic benefits, including reduced toxicity and minimized side effects. This study highlights niosomes as a versatile platform with the potential to transform drug delivery across a variety of therapeutic areas. Their controlled release, stability enhancement, and targeted delivery capabilities position them as valuable tools for future medical applications. Ongoing advancements in green synthesis and surface modification are expected to further refine their efficacy and expand their clinical applications. Niosomes are small, effective carriers that protect drugs and release them gradually, targeting specific areas in the body to make treatments safer and more efficient. This study explores the benefits of niosomes and emphasizes sustainable, environmentally friendly methods of production, supporting their use in future healthcare.

Vasilyeva Leysan A., Gaynanova Gulnara A., Romanova Elvira A., Petrov Konstantin A., Feng Chuanliang, Zakharova Lucia Ya., Sinyashin Oleg G.

Diabetes and its complications derived are among serious global health concerns that critically deteriorate the quality of life of patients and, in some cases, result in lethal outcome. Herein, general information on the pathogenesis, factors aggravating the course of the disease and drugs used for the treatment of two types of diabetes are briefly discussed. The aim of the review is to introduce supramolecular strategies that are currently being developed for the treatment of diabetes mellitus and that present a very effective alternative to chemical synthesis, allowing the fabrication of nanocontainers with switchable characteristics that meet the criteria of green chemistry. Particular attention is paid to organic (amphiphilic and polymeric) formulations, including those of natural origin, due to their biocompatibility, low toxicity, and bioavailability. The advantages and limitations of different nanosystems are discussed, with emphasis on their adaptivity to noninvasive administration routes. The bibliography includes 378 references.

Shirokikh A.D., Fenin A.A., Koroleva M.Y.

Lipid nanoparticles such as nanoemulsions, nanostructured and solid lipid particles made of stearic acid and paraffin oil and stabilized with a mixture of nonionic surfactants Tween 60 and Span 60 are studied. The effect of incorporated yttrium stearate (YSt) as an additive in the modelling of radiopharmaceuticals and radiotherapy on the physicochemical properties of lipid nanoparticles is considered. The resultes indicate that the size of the oil droplets changes slightly when YSt is included in the nanoemulsions. The incorporation of YSt into lipid nanoparticles with stearic acid reduces their size, due apparently to the incorporation of YSt into the adsorption layer together with stearic acid. The studied lipid nanoparticles are resistant to radioactive irradiation with a dose of 5 kGy. No changes in the molecular structure of the components are observed after irradiation, and the aggregative stability of the lipid nanoparticles is not changed.

Kim S.

Vitamin E is a fat-soluble vitamin with several forms. Among these, α-tocopherol (TOC) is preferentially absorbed and accumulated in humans. In the body, it acts as an antioxidant, helping to protect cells from the damage caused by free radicals. It is an organic chemical compound that undergoes degradation upon irradiation with UV light. To protect this bioactive chemical compound from UV light degradation, encapsulation was carried out using zein as a shell material. Due to the unique phase diagram of TOC in aqueous ethanol, the encapsulation efficiency was >99%. The size of encapsulated particles was ~300 nm or smaller, and the thickness of the shell wall was ~30 nm. The presented procedure offers the most simple and efficient encapsulation process that yields edible products. The investigation of the irradiation effect of UV on TOC revealed that the encapsulation effectively blocks UV light and prevents TOC from being degraded. The presented procedure offers an instantaneous and highly efficient encapsulation process, which yields edible products.

Romeo M., Hafidi Z., Muzzalupo R., Pons R., García M.T., Mazzotta E., Pérez L.

Background: This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based surfactants from phenylalanine), with a focus on physicochemical characterization and the evaluation of antimicrobial and cytotoxic properties. Method: Phenylalanine surfactants were characterized via high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Different niosomal systems based on capsaicin, lidocaine, cationic phenylalanine surfactants, and dipalmitoyl phosphatidylcholine (DPPC) were characterized in terms of size, polydispersion index (PI), zeta potential, and encapsulation efficiency using dynamic light scattering (DLS), transmitted light microscopy (TEM), and small-angle X-ray scattering (SAXS). Furthermore, the interaction of the pure compounds used to prepare the niosomal formulations with DPPC monolayers was determined using a Langmuir balance. The antibacterial activity of the vesicular systems and their biocompatibility were evaluated, and molecular docking studies were carried out to obtain information about the mechanism by which these compounds interact with bacteria. Results: The stability and reduced size of the analyzed niosomal formulations demonstrate their potential in pharmaceutical applications. The nanosystems exhibit promising antimicrobial activity, marking a significant advancement in pharmaceutical delivery systems with dual therapeutic properties. The biocompatibility of some formulations underscores their viability. Conclusions: The proposed niosomal formulations could constitute an important advance in the pharmaceutical field, offering delivery systems for combined therapies thanks to the pharmacological properties of the individual components.

Poustforoosh A.

Niosomes are versatile nanocarriers for therapeutic compounds, and optimizing their structures via ionic surfactants can enhance their functionality considerably. Catanionic niosomes, which have the capability of both cationic and anionic niosomes, are attractive vehicles for drug delivery objectives. Here, we aim to design and evaluate catanionic niosome as a vehicle for anticancer agents. A molecular modeling pipeline was performed to model the physicochemical properties of cationic, anionic, and catanionic niosomes as a multifunctional drug delivery system for Cabozantinib. SPAN60 was used as the nonionic surfactant, cholesterol was the stabilizer, DOTAP and DCP were used as the cationic and anionic surfactants, respectively, and cabozantinib, an FDA-approved c-Met inhibitor was chosen as the drug compound. Some meaningful parameters relevant to the cabozantinib molecule and its characteristics in the bilayer, such as hydrogen bonding, total energy, the radius of gyration (Rgyr), mean square displacements (MSD), diffusion coefficient, and the radial distribution function (RDF) were evaluated and compared between the formulations. The outcomes revealed that hydrogen bonding of cabozantinib is more probable with DOTAP, and the total energy of the drug is lower in anionic formulation (-180 kcal/mol). The MSD showed that cationic niosome restricts the movement of cabozantinib, while the drug could be efficiently released from the anionic niosome, and catanionic niosome can equilibrate the movement of the drug with a diffusion coefficient of 5.73 × 10-12 (m2/s). This technique could effectively describe the behavior of drugs in various bilayer compositions, and the catanionic niosomes are potential multifunctional carriers for anticancer agents.

Mǎgeruşan L., Pogǎcean F., Cozar B., Tripon S., Pruneanu S.

Increased evidence has documented a direct association between Ciprofloxacin (CFX) intake and significant disruption to the normal functions of connective tissues, leading to severe health conditions (such as tendonitis, tendon rupture and retinal detachment). Additionally, CFX is recognized as a potential emerging pollutant, as it seems to impact both animal and human food chains, resulting in severe health implications. Consequently, there is a compelling need for the precise, swift and selective detection of this fluoroquinolone-class antibiotic. Herein, we present a novel graphene-based electrochemical sensor designed for Ciprofloxacin (CFX) detection and discuss its practical utility. The graphene material was synthesized using a relatively straightforward and cost-effective approach involving the electrochemical exfoliation of graphite, through a pulsing current, in 0.05 M sodium sulphate (Na2SO4), 0.05 M boric acid (H3BO3) and 0.05 M sodium chloride (NaCl) solution. The resulting material underwent systematic characterization using scanning electron microscopy/energy dispersive X-ray analysis, X-ray powder diffraction and Raman spectroscopy. Subsequently, it was employed in the fabrication of modified glassy carbon surfaces (EGr/GC). Linear Sweep Voltammetry studies revealed that CFX experiences an irreversible oxidation process on the sensor surface at approximately 1.05 V. Under optimal conditions, the limit of quantification was found to be 0.33 × 10−8 M, with a corresponding limit of detection of 0.1 × 10−8 M. Additionally, the developed sensor’s practical suitability was assessed using commercially available pharmaceutical products.

Kushnazarova R.A., Mirgorodskaya A.B., Bekrenev D.D., Lyubina A.P., Lenina O.A., Petrov K.A., Voloshina A.D., Zakharova L.Y.

The aggregation behavior of mixed micellar solutions based on 2-hydroxyethylpiperidinium surfactants and nonionic surfactant Brij® 35 was investigated. The critical micelle concentrations determined by varying the component ratio suggest a negative deviation from the ideal mixing model (synergistic effect). It was demonstrated that the magnitude of the deviation from ideal mixing behavior depends on the alkyl chain length in the cationic surfactant and on the component ratio. The solubilization effect of the binary systems on hydrophobic substances was evaluated taking Orange OT dye and ibuprofen drug as examples. It was found that the piperidinium surfactants studied, both individually and in compositions containing up to 50% of the nonionic surfactant, exhibit high antimicrobial activity comparable to that of commercial antibiotics.

Rambo M.K., Lins R.F., Silva F.L., Alonso A., Rambo M.C., Leal J.E., Sousa-Neto D.D.

Abstract Colloidal systems have been used to encapsulate, protect and release essential oils in mouthwashes. In this study, we investigated the effect of cetylpyridinium chloride (CPC) on the physicochemical properties and antimicrobial activity of oil-in-water colloidal systems containing tea tree oil (TTO) and the nonionic surfactant polysorbate 80. Our main aim was to evaluate whether CPC could improve the antimicrobial activity of TTO, since this activity is impaired when this essential oil is encapsulated with polysorbate 80. These systems were prepared with different amounts of TTO (0-0.5% w/w) and CPC (0-0.5% w/w), at a final concentration of 2% (w/w) polysorbate 80. Dynamic light scattering (DLS) results revealed the formation of oil-swollen micelles and oil droplets as a function of TTO concentration. Increases in CPC concentrations led to a reduction of around 88% in the mean diameter of oil-swollen micelles. Although this variation was of only 20% for the oil droplets, the samples appearance changed from turbid to transparent. The surface charge of colloidal structures was also markedly affected by the CPC as demonstrated by the transition in zeta potential from slightly negative to highly positive values. Electron paramagnetic resonance (EPR) studies showed that this transition is followed by significant increases in the fluidity of surfactant monolayer of both colloidal structures. The antimicrobial activity of colloidal systems was tested against a Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureaus) bacteria. Our results revealed that the inhibition of bacterial growth is observed for the same CPC concentration (0.05% w/w for E. coli and 0.3% w/w for S. aureus) regardless of TTO content. These findings suggest that TTO may not act as an active ingredient in polysorbate 80 containing mouthwashes.

Liga S., Paul C., Moacă E., Péter F.

Niosomes are vesicular nanocarriers, biodegradable, relatively non-toxic, stable, and inexpensive, that provide an alternative for lipid-solid carriers (e.g., liposomes). Niosomes may resolve issues related to the instability, fast degradation, bioavailability, and insolubility of different drugs or natural compounds. Niosomes can be very efficient potential systems for the specific delivery of anticancer, antioxidant, anti-inflammatory, antimicrobial, and antibacterial molecules. This review aims to present an overview of their composition, the most common formulation techniques, as well as of recent utilizations as delivery systems in cancer therapy.

Zhiltsova E.P., Valeeva F.G., Kuznetsov D.M., Kushnazarova R.A., Vasilieva E.A., Mirgorodskaya A.B., Zakharova L.Y.

The hydrolytic decomposition of the organophosphorus ecotoxicant paraoxon in alkaline micellar solutions of a cationic surfactant with a carbamate fragment (CB-2-16) has been investigated by means of spectrophotometry. The stronger catalytic effect of micellar solutions aged during several days in comparison with freshly prepared ones has been associated with alkaline hydrolysis of the carbamate surfactant and the formation of a mixed system of CB-2-16 with its decomposition product cetyl(2-hydroxyethyl)dimethylammonium bromide (1H NMR spectroscopy data). In the absence of alkali, the decomposition products of the carbamate surfactant have not been detected for more than four months, indicating its hydrolytic stability in a neutral environment.

Faddah H., Nsairat H., Shalan N.M., El-Tanani M., Alqudah D.A., Alshaer W.

AbstractDoxorubicin (DOX) is widely used against solid tumors. Niosomes are self‐assembled nanocarriers of non‐ionic surfactants. DOX loaded into cationic niosomes (DOX−Nio) was prepared via thin film hydration method. DOX−Nio was then decorated with a hyaluronic acid (DOX−HA−Nio) via electrostatic interaction. DOX−Nio and DOX−HA−Nio displayed a particle size of 120.0±1.02 and 182.9±2.3 nm, and charge of + 35.5±0.15 and −15.6±0.25 mV, respectively, with PDI < 0.3. DOX−HA−Nio showed a good stability regarding size and charge over 4 weeks at 4 °C and maintain their integrity after lyophilization. HPLC results showed a 94.1±4.2 % encapsulation efficiency of DOX with good entrapment and slow, prolonged DOX release even after 48 hrs. Cell viability assay showed an IC50 of 14.26 nM for the DOX−HA−Nio against MCF‐7 cell line with micromolar IC50 results against CD‐44 negative cell lines (NIH/3T3). DOX−HA−Nio was proven to be an effective, targeted nanocarrier for DOX against MCF‐7 cell line.

Lu Z., Mahony A.K., Arnold W., Marshall C., McNamara P.

Quaternary ammonium compounds (QACs) are a class of compounds that were widely used as disinfectants during the COVID-19 pandemic and continue to be used as disinfecting agents. After consumer usage,...

Hong S.E., Lee J., Lee H.G.

The potential of multi-layer nanoemulsions (NEs) for improving the cellular uptake, antioxidant activity, and in vitro bioaccessibility of α-tocopherol (ToC) was examined. ToC-loaded multi-layer NEs were prepared using lecithin (primary-NEs, P-NEs), chitosan (secondary-NEs, S-NEs), and dextran sulfate (tertiary-NEs, T-NEs) as wall materials. The bioadhesion, cellular permeability, and uptake of the multi-layer NEs were significantly higher than that of the free coumarin 6 (C6). As a result of cellular uptake, the mean fluorescence intensity of T-NEs was the highest among the three types of multi-layer NEs and was 9.8-fold higher than that of free C6. The cellular antioxidant abilities of P-NEs, S-NEs, and T-NEs were 40, 45, and 50 %, respectively. Multi-layer nanoencapsulation sustains free fatty acid release after digestion. Moreover, the bioavailability of T-NEs exhibited a two-fold increase compared with that of the free ToC. These findings indicate that by multi-layer NEs using a layer-by-layer method, the cellular uptake, in vitro bioaccessibility, and antioxidant activity of ToC can be improved. Furthermore, T-NEs using chitosan and dextran sulfate can potentially enhance the cellular uptake, in vitro bioaccessibility, and antioxidant activity of ToC. These findings would facilitate the application of multi-layer NEs for lipophilic bioactive compounds using biopolymers.

Nunes B., Cagide F., Fernandes C., Borges A., Borges F., Simões M.

Antibacterial resistance poses a critical public health threat, challenging the prevention and treatment of bacterial infections. The search for innovative antibacterial agents has spurred significant interest in quaternary heteronium salts (QHSs), such as quaternary ammonium and phosphonium compounds as potential candidates. In this study, a library of 49 structurally related QHSs was synthesized, varying the cation type and alkyl chain length. Their antibacterial activities against Staphylococcus aureus, including antibiotic-resistant strains, were evaluated by determining minimum inhibitory/bactericidal concentrations (MIC/MBC) ≤ 64 µg/mL. Structure–activity relationship analyses highlighted alkyl-triphenylphosphonium and alkyl-methylimidazolium salts as the most effective against S. aureus CECT 976. The length of the alkyl side chain significantly influenced the antibacterial activity, with optimal chain lengths observed between C10 and C14. Dose–response relationships were assessed for selected QHSs, showing dose-dependent antibacterial activity following a non-linear pattern. Survival curves indicated effective eradication of S. aureus CECT 976 by QHSs at low concentrations, particularly compounds 1e, 3e, and 5e. Moreover, in vitro human cellular data indicated that compounds 2e, 4e, and 5e showed favourable safety profiles at concentrations ≤ 2 µg/mL. These findings highlight the potential of these QHSs as effective agents against susceptible and resistant bacterial strains, providing valuable insights for the rational design of bioactive QHSs.

Schreiner T.B., Santamaria-Echart A., Colucci G., Plasencia P., Patrícia Santos Costa P., Dias M.M., Pinho S.P., Filomena Barreiro M.

Nanoemulsions can be produced using simple methods and compounds from natural sources. They can increase water dispersibility and bioavailability and optimise active ingredient dispersion in particular skin layers. Lipophilic compounds of the vitamin E family (tocopherols and tocotrienols) are well-known for their high antioxidant activity and capacity to protect the skin from oxidative stress. In this context, oil-in-water (o/w) nanoemulsions with and without α-tocopherol (Vitamin E, VE) were formulated with two emulsifier alternatives, Quillaja saponin (QS), and a combination of QS with Tribulus terrestris (QSTT) (50/50, w/w). The emulsions were evaluated concerning stability, microstructure, droplet size, colour attributes, encapsulation efficiency, UV photostability, antioxidant activity, and in vitro permeation studies to assess the delivery potential. Results showed highly stable systems, with round-shape droplets of 80–121 nm size. QS and QSTT samples' colours were close to white and light brownish, respectively. The topical nano cream had the capacity to entrap VE, producing a protective effect from UV degradation, and very significant antioxidant activity, with IC50 values around 0.01 %wt. The skin permeation profiles showed the efficiency of the formulations in the delivery of VE, with permeabilities between 64 and 74 µg/cm2, while the control sample showed no VE permeation.

Yuan Y., Wang Z., Su S., Lin C., Mi Y., Tan W., Guo Z.

New amphiphilic low molecular weight chitosan-graft-nicotinic acid bearing decyl groups (LCND) was synthesized by two-step reaction and spontaneously assembled into cationic micelle by ultra-sonication method to improve water solubility and photostability properties of α-tocopherol. The chemical structure of LCND was characterized and physical properties of cationic micelle were evaluated. Results displayed that cationic micelle exhibited strong self-assemble ability with nanoscale spherical morphology and showed best loading ability with loading content of 18.50% when the feeding ratio of LCND to α-tocopherol reached 10:3. Meanwhile, the greatly enhanced water solubility, photostability and sustained release behavior of α-tocopherol in cationic micelle were observed. The cumulative release of α-tocopherol in cationic micelle reached up 82.18% within 96 h while free α-tocopherol was completely released within 10 h. Additionally, release kinetics models were also fitted. The LCND cationic micelle could be promising nanocarrier for improving the physicochemical properties of α-tocopherol in food fields.

Pires P.C., Paiva-Santos A.C., Veiga F.

Psychiatric and neurodegenerative disorders are amongst the most prevalent and debilitating diseases, but current treatments either have low success rates, greatly due to the low permeability of the blood–brain barrier, and/or are connected to severe side effects. Hence, new strategies are extremely important, and here is where liposome-derived nanosystems come in. Niosomes, transfersomes, and ethosomes are nanometric vesicular structures that allow drug encapsulation, protecting them from degradation, and increasing their solubility, permeability, brain targeting, and bioavailability. This review highlighted the great potential of these nanosystems for the treatment of Alzheimer’s disease, Parkinson’s disease, schizophrenia, bipolar disorder, anxiety, and depression. Studies regarding the encapsulation of synthetic and natural-derived molecules in these systems, for intravenous, oral, transdermal, or intranasal administration, have led to an increased brain bioavailability when compared to conventional pharmaceutical forms. Moreover, the developed formulations proved to have neuroprotective, anti-inflammatory, and antioxidant effects, including brain neurotransmitter level restoration and brain oxidative status improvement, and improved locomotor activity or enhancement of recognition and working memories in animal models. Hence, albeit being relatively new technologies, niosomes, transfersomes, and ethosomes have already proven to increase the brain bioavailability of psychoactive drugs, leading to increased effectiveness and decreased side effects, showing promise as future therapeutics.