New piperidinium surfactants with carbamate fragments as effective adjuvants in insecticide compositions based on imidacloprid.

BACKGROUND: Surfactants, 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. RESULTS: The 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. CONCLUSION: The 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.

Piperidinium surfactants functionalized with carbamate fragment: Aggregation, antimicrobial activity and cytotoxicity.

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.

Supramolecular Tools to Improve Wound Healing and Antioxidant Properties of Abietic Acid: Biocompatible Microemulsions and Emulgels.

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.

Microemulsions and nanoemulsions modified with cationic surfactants for improving the solubility and therapeutic efficacy of loaded drug indomethacin.

In this work, a noncovalent strategy was successfully used to modify colloidal stability andin vitroandin vivoefficacy of two amphiphilic formulations of the anti-inflammatory drug indomethacin. Namely, nanoemulsions and microemulsions based on oleic acid and nonionic surfactants have been produced and compared. The influence of cationic surfactants cetyltrimethylammonium bromide and its carbamate bearing analogue on the size characteristics, stability and ability to provide prolonged action of loaded drug indomethacin has been evaluated. Adding the positively charged molecules in the surface layer of nanoemulsions and microemulsions has shown the stability increase along with maintaining the size characteristics and homogeneity in time. Moreover, the carbamate modified analogue demonstrated beneficial behavior. Indomethacin loaded in microemulsions and nanoemulsions showed prolonged-release (10%-15% release for 5 h) compared to a free drug (complete release for 5 h). The rate of release of indomethacin from nanoemulsions was slightly higher than from microemulsions and insignificantly decreased with an increase in the concentration of the cationic surfactant. For carbamate surfactant nanocarrier loaded with fluorescence probe Nile Red, the ability to penetrate into the cell was supported by flow cytometry study and visualized by fluorescence microscopy.In vitrotests on anti-inflammatory activity of the systems demonstrated that the blood cell membrane stabilization increased in the case of modified microemulsion. The anti-inflammatory activity of the encapsulated drug was tested in rats using a carrageenan-induced edema model. Nanoemulsions without cationic surfactants appeared more efficient compared to microemulsions. Indomethacin emulsion formulations with carbamate surfactant added showed slower carrageenan-induced edema progression compared to unmodified compositions. Meanwhile, the edema completely disappeared upon treatment with emulsion loaded indomethacin after 4 h in the case of microemulsions versus 5 h in the case of nanoemulsions.

Antimicrobial Properties and Cytotoxic Effect of Imidazolium Geminis with Tunable Hydrophobicity.

Antimicrobial, membranotropic and cytotoxic properties of dicationic imidazolium surfactants of n-s-n (Im) series with variable length of alkyl group (n = 8, 10, 12, 14, 16) and spacer fragment (s = 2, 3, 4) were explored and compared with monocationic analogues. Their activity against a representative range of Gram-positive and Gram-negative bacteria, and also fungi, is characterized. The relationship between the biological activity and the structural features of these compounds is revealed, with the hydrophobicity emphasized as a key factor. Among dicationic surfactants, decyl derivatives showed highest antimicrobial effect, while for monocationic analogues, the maximum activity is observed in the case of tetradecyl tail. The leading compounds are 2-4 times higher in activity compared to reference antibiotics and prove effective against resistant strains. It has been shown that the antimicrobial effect is not associated with the destruction of the cell membrane, but is due to specific interactions of surfactants and cell components. Importantly, they show strong selectivity for microorganism cells while being of low harm to healthy human cells, with a SI ranging from 30 to 100.

Self-Assembling Drug Formulations with Tunable Permeability and Biodegradability.

This review focuses on key topics in the field of drug delivery related to the design of nanocarriers answering the biomedicine criteria, including biocompatibility, biodegradability, low toxicity, and the ability to overcome biological barriers. For these reasons, much attention is paid to the amphiphile-based carriers composed of natural building blocks, lipids, and their structural analogues and synthetic surfactants that are capable of self-assembly with the formation of a variety of supramolecular aggregates. The latter are dynamic structures that can be used as nanocontainers for hydrophobic drugs to increase their solubility and bioavailability. In this section, biodegradable cationic surfactants bearing cleavable fragments are discussed, with ester- and carbamate-containing analogs, as well as amino acid derivatives received special attention. Drug delivery through the biological barriers is a challenging task, which is highlighted by the example of transdermal method of drug administration. In this paper, nonionic surfactants are primarily discussed, including their application for the fabrication of nanocarriers, their surfactant-skin interactions, the mechanisms of modulating their permeability, and the factors controlling drug encapsulation, release, and targeted delivery. Different types of nanocarriers are covered, including niosomes, transfersomes, invasomes and chitosomes, with their morphological specificity, beneficial characteristics and limitations discussed.