Natural deep eutectic solvents (NaDES) represent a new generation of green, non-flammable solvents, useful as an efficient alternative to the well-known ionic liquids. They can be easily prepared and exhibit unexpected solubilizing power for lipophilic molecules, although those of a hydrophilic nature are mostly used. For their unique properties, they can be recommend for different cosmetic and pharmaceutical applications, ranging from sustainable extraction, obtaining ready-to-use ingredients, to the development of biocompatible drug delivery responsive systems. In the biomedical field, NaDES can be used as biopolymer modifiers, acting as delivery compounds also known as “therapeutic deep eutectic systems”, being able to solubilize and stabilize different chemical and galenical formulations. The aim of this review is to give an overview of the current knowledge regarding natural deep eutectic solvents specifically applied in the cosmetic and pharmaceutical fields. The work could help to disclose new opportunities and challenges for their implementation not only as green alternative solvents but also as potential useful pathways to deliver bioactive ingredients in innovative formulations.

The production of olive oil generates olive mill wastewater (OMW) which essentially derives from the processing, treatment and pressing of olives in mills. Traditional milling processes require a quantity of water varying between 40 and 120 L per quintal of pressed olives, generating a considerable amount of wastewater. It is thus necessary to reduce process water and enhance its use to implement the concept of a circular economy. To this end, our preliminary work was dedicated to water purification by means of suitable and efficient filtration systems. The microfiltered OMW was firstly concentrated through reverse osmosis. Then, an additional concentration step was carried out via vacuum membrane distillation using hydrophobic hollow fiber membranes. The application of the membrane-based processes allowed the recovery of a purified water and the concentration of valuable polyphenols in a smaller volume. The different fractions obtained from the purification have been tested for the determination of the antioxidant power (DPPH assay) and dosage of polyphenols (Folin–Ciocalteu assay) and were characterized using IR spectroscopy. All samples showed relevant antioxidant activity (percentage range: 10–80%) and total phenolic content in the 1.5–15 g GAE/L range. The obtained fractions were tested for their antimicrobial effect on numerous clinical isolates of Gram-positive and Gram-negative species, resistant and multi-resistant to current antibiotic drugs. OMW samples showed widespread activity against the considered (phyto)pathogens (MIC range 8–16 mg/mL) thus supporting the value of this waste material in the (phyto)pharmaceutical field.

Multi-drug resistant bacterial strains (MDR) have become an increasing challenge to our health system, resulting in multiple classical antibiotics being clinically inactive today. As the de-novo development of effective antibiotics is a very costly and time-consuming process, alternative strategies such as the screening of natural and synthetic compound libraries is a simple approach towards finding new lead compounds. We thus report on the antimicrobial evaluation of a small collection of fourteen drug-like compounds featuring indazoles, pyrazoles and pyrazolines as key heterocyclic moieties whose synthesis was achieved in continuous flow mode. It was found that several compounds possessed significant antibacterial potency against clinical and MDR strains of the Staphylococcus and Enterococcus genera, with the lead compound (9) reaching MIC values of 4 µg/mL on those species. In addition, time killing experiments performed on compound 9 on Staphylococcus aureus MDR strains highlight its activity as bacteriostatic. Additional evaluations regarding the physiochemical and pharmacokinetic properties of the most active compounds are reported and showcased, promising drug-likeness, which warrants further explorations of the newly identified antimicrobial lead compound.

Multidrug resistance (MDR) among pathogens and the associated infections represent an escalating global public health problem that translates into raised mortality and healthcare costs. MDR bacteria, with both intrinsic abilities to resist antibiotics treatments and capabilities to transmit genetic material coding for further resistance to other bacteria, dramatically decrease the number of available effective antibiotics, especially in nosocomial environments. Moreover, the capability of several bacterial species to form biofilms (BFs) is an added alarming mechanism through which resistance develops. BF, made of bacterial communities organized and incorporated into an extracellular polymeric matrix, self-produced by bacteria, provides protection from the antibiotics’ action, resulting in the antibiotic being ineffective. By adhering to living or abiotic surfaces present both in the environment and in the healthcare setting, BF causes the onset of difficult-to-eradicate infections, since it is difficult to prevent its formation and even more difficult to promote its disintegration. Inspired by natural antimicrobial peptides (NAMPs) acting as membrane disruptors, with a low tendency to develop resistance and demonstrated antibiofilm potentialities, cationic polymers and dendrimers, with similar or even higher potency than NAMPs and with low toxicity, have been developed, some of which have shown in vitro antibiofilm activity. Here, aiming to incite further development of new antibacterial agents capable of inhibiting BF formation and dispersing mature BF, we review all dendrimers developed to this end in the last fifteen years. The extension of the knowledge about these still little-explored materials could be a successful approach to find effective weapons for treating chronic infections and biomaterial-associated infections (BAIs) sustained by BF-producing MDR bacteria.

Untreatable infections, growing healthcare costs, and increasing human mortality due to the rising resistance of bacteria to most of the available antibiotics are global phenomena that urgently require the discovery of new and effective antimicrobial agents. Cationic macromolecules, acting as membrane disruptors, are widely studied, and several compounds, including two styrene-based copolymers developed by us (P5 and P7), have proved to possess potent broad-spectrum antibacterial effects, regardless of the resistance profiles of the bacteria. Here, we first reported the synthesis and physicochemical characterization of new cationic nanoparticles (NPs) (CP1 and OP2), obtained by polymerizing the monomers 4-ammoniummethylstyrene (4-AMSTY) and 4-ammoniumethylstyrene (4-AESTY) hydrochlorides, whose structures were designed using the cationic monomers of P5 and P7 as template compounds. The antibacterial activity of CP1 and OP2 was assessed against several Gram-positive and Gram-negative multi-drug resistant (MDR) pathogens, observing potent antibacterial effects for both CP1 (MICs = 0.1–0.8 µM) and OP2 (MICs = 0.35–2.8 µM) against most of the tested isolates. Additionally, time-killing studies carried out with CP1 and OP2 on different strains of the most clinically relevant MDR species demonstrated that they kill pathogens rapidly. Due to their interesting physicochemical characteristics, which could enable their mutual formulation as hydrogels, CP1 and OP2 could represent promising ingredients for the development of novel antibacterial dosage forms for topical applications, capable of overcoming severe infections sustained by bacteria resistant to the presently available antibiotics.

Although the antimicrobial potency of the pyrazole nucleus is widely reported, the antimicrobial effects of the 2-(4-bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4), found to be active against several other conditions, have never been investigated. Considering the worldwide need for new antimicrobial agents, we thought it noteworthy to assess the minimum inhibitory concentration (MICs) of BBB4 but, due to its scarce water-solubility, unequivocal determinations were tricky. To obtain more reliable MICs and to obtain a substance also potentially applicable in vivo, we recently prepared water-soluble, BBB4-loaded dendrimer nanoparticles (BBB4-G4K NPs), which proved to have physicochemical properties suitable for clinical application. Here, with the aim of developing a new antibacterial agent based on BBB4, the BBB4-G4K NPs were tested on several strains of different species of the Staphylococcus genus. Very low MICs (1.5–3.0 µM), 15.5–124.3-fold lower than those of the free BBB4, were observed against several isolates of S. aureus and S. epidermidis, the most pathogenic species of this genus, regardless of their resistance patterns to antibiotics. Aiming at hypothesizing a clinical use of BBB4-G4K NPs for staphylococcal skin infections, cytotoxicity experiments on human keratinocytes were performed; it was found that the nano-manipulated BBB4 released from BBB4-G4K NPs (LD₅₀ 138.6 µM) was 2.5-fold less cytotoxic than the untreated BBB4 (55.9 µM). Due to its physicochemical and biological properties, BBB4-G4K NPs could be considered as a promising novel therapeutic option against the very frequent staphylococcal skin infections.