Olivier Jean Cayre

As the global rise in antimicrobial resistance calls for new therapeutic strategies, synthetic antimicrobial polymers (SAMPs) have emerged as promising alternatives to host-defense peptides, offering tunable structures and reduced limitations. In this work, we employed machine learning (ML) approaches to elucidate the structure–activity relationships of a library of polyacrylamides systematically varied in (1) amine side-chain chemistry, (2) chain length, (3) cationic amine ratio, and (4) polymer architecture. The library consisted of 23 different polymer designs, 3 of which exhibited low minimum inhibitory concentrations (MIC) against different bacterial strains, and 5 of which caused low red blood cells agglutination. Among the evaluated ML algorithms, regression random forest and gradient boosting regression consistently reproduced feature importance and maintained stable decision-tree structures, with gradient boosting outperforming random forest in predictive power. Gradient boosting achieved RSME values of 20, 6, 13 and 12 μg/ml, respectively, for each modelled MIC of 4 bacterial strains: Pseudomonas aeruginosa PA14, Pseudomonas aeruginosa LESB58, Staphylococcus aureus USA300 and Staphylococcus aureus Newman (total data range 64-513 μg/ml). RSME for modelled hemagglutination was 1 μg/ml. Calculation of feature importances and visualisation with beeswarm and waterfall plots highlighted the contribution of individual polymer features through Shapley additive explanations (SHAP). All bacteria strains considered, the type and percentage of cationic monomer are the most important features determining best-performing SAMP designs. Collectively, our findings demonstrate that boosting-ensemble methods offer consistent robust predictive capability and can serve as effective tools for forecasting the potency and toxicity of future SAMP designs, with potential for application in larger, multi-sourced libraries.

Nonspherical degradable microcapsules formed from a dry liquid based Pickering emulsion template via interfacial anionic polymerisation.

This study introduces an eco-friendly approach to fabricating superstrong, core-shell, composite microcapsules, offering a sustainable alternative to traditional insoluble microplastic-based materials like melamine-formaldehyde. These microcapsules were engineered with a thick CaCO₃ shell formed via crystal ripening in the presence of water-soluble poly(acrylic acid), encasing a hexylsalicylate oil core armored by hydrophilic SiO₂ nanoparticles. An additional polydopamine layer was deposited via oxidative autopolymerization at pH 8.5 for improved structural and surface properties of the resulting microcapsules. These microcapsules (D _3,2 = 8.8 ± 0.3 μm) were spherical, with a relatively smooth surface, and exhibited unique mechanical properties, which are essential to broaden their applications in industry. Remarkably, compression tests showed a mean rupture stress of 73.5 ± 5.0 MPa, which dramatically surpasses any other inorganic/synthetic microcarrier reported in the literature. In addition, only 10-20% of the core active was released within 2 h into a mixed water-propanol medium used as an accelerated release test, where the solubility of the active oil is high, with full release over 3 days. Herein, we also propose a novel pathway-specific binding constant (PSBC) that describes the strong interaction between Ca²⁺ ions and poly(acrylic acid), in connection with their stoichiometric ratio. Overall, these microcapsules hold promise for multiple fast-moving consumer goods, where maximizing the mechanical strength of microcapsules for encapsulation of valuable functional actives is paramount; this includes but is not limited to energy storage, household, agrochemical, personal care, and healthcare applications.

Summary: Transmission electron microscopy can be used for the characterisation of a wide range of thin specimens, but soft matter and aqueous samples such as gels, nanoparticle dispersions, and emulsions will dry out and collapse under the microscope vacuum, therefore losing information on their native state and ultimately limiting the understanding of the sample.This study examines commonly used techniques in transmission electron microscopy when applied to the characterisation of cryogenically frozen Pickering emulsion samples. Oil‐in‐water Pickering emulsions stabilised by 3 to 5 nm platinum nanoparticles were cryogenically frozen by plunge‐freezing into liquid ethane to retain the native structure of the system without inducing crystallisation of the droplet oil cores.A comparison between the droplet morphology following different sample preparation methods has confirmed the effectiveness of using plunge‐freezing to prepare these samples. Scanning transmission electron microscopy imaging showed that dry droplets collapse under the microscope vacuum, changing their shape and size (average apparent diameter: ∼342 nm) compared to frozen samples (average diameter: ∼183 nm). Cryogenic electron tomography was used to collect additional information of the 3D shape and size of the emulsion droplets, and the position of the stabilising nanoparticles relative to the droplet surface. Cryogenic energy dispersive X‐ray and electron energy loss spectroscopy were used to successfully obtain elemental data and generate elemental maps to identify the stabilising nanoparticles and the oil phase. Elemental maps generated from spectral data were used in conjunction with electron tomography to obtain 3D information of the oil phase in the emulsion droplets.Beam‐induced damage to the ice was the largest limiting factor to the sample characterisation, limiting the effective imaging resolution and signal‐to‐noise ratio, though careful consideration of the imaging parameters used allowed for the characterisation of the samples presented in this study. Ultimately this study shows that cryo‐methods are effective for the representative characterisation of Pickering emulsions.

Preparation of multicore silica microcapsules containing a lipid-soluble vitamin for potential cosmetic applications.

To form nonspherical emulsion droplets, the interfacial tension driving droplet sphericity must be overcome. This can be achieved through interfacial particle jamming; however, careful control of particle coverage is required. In this work, we present a scalable novel batch process to form nonspherical particle-stabilized emulsions. This is achieved by concurrently forming interfacially active particles and drastically accelerating emulsion destabilization through addition of electrolyte. To achieve this, surfactant-stabilized oil-in-water emulsions in the presence of dopamine were first produced. These emulsions were then treated with tris(hydroxymethyl)aminomethane hydrochloride buffer to both simultaneously initiate polymerization of dopamine in the emulsion continuous phase and reduce the Debye length of the system, thus accelerating droplet coalescence while forming surface-active particles. The concentration of buffer and imposed shear was then systematically varied, and the behavior at the interface was studied using pendent drop tensiometry and interfacial shear rheology. It was found that polydopamine nanoparticles formed in the emulsion continuous phase adsorbed to the reducing interface during coalescence, resulting in anisotropic droplets formed via arrested coalescence. Greater shear rates resulted in accelerated coalescence and formation of secondary droplets, whereas lower shear rates resulted in thicker interfacial films. The efficacy of this method was further demonstrated with a second system consisting of sodium dodecyl sulfate as the surfactant and polypyrrole particles, which also resulted in nonspherical droplets for optimized conditions.

Programmable synthesis of polymer nanoparticles prepared by polymerization-induced self-assembly (PISA) mediated by reversible addition-fragmentation chain-transfer (RAFT) dispersion polymerization with specified diameter is achieved in an automated flow-reactor platform. Real-time particle size and monomer conversion is obtained via inline spatially resolved dynamic light scattering (SRDLS) and benchtop nuclear magnetic resonance (NMR) instrumentation. An initial training experiment generated a relationship between copolymer block length and particle size for the synthesis of poly(N,N-dimethylacrylamide)-b-poly(diacetone acrylamide) (PDMAm-b-PDAAm) nanoparticles. The training data was used to target the product compositions required for synthesis of nanoparticles with defined diameters of 50, 60, 70, and 80 nm, while inline NMR spectroscopy enabled rapid acquisition of kinetic data to support their scale-up. NMR and SRDLS were used during the continuous manufacture of the targeted products to monitor product consistency while an automated sampling system collected practically useful quantities of the targeted products, thus outlining the potential of the platform as a tool for discovery, development, and manufacture of polymeric nanoparticles.

Microencapsulation is an advanced methodology for the protection, preservation, and/or delivery of active materials in a wide range of industrial sectors, such as pharmaceuticals, cosmetics, fragrances, paints, coatings, detergents, food products, and agrochemicals. Polymeric materials have been extensively used as microcapsule shells to provide appropriate barrier properties to achieve controlled release of the encapsulated active ingredient. However, significant limitations are associated with such capsules, including undesired leaching and the nonbiodegradable nature of the typically used polymers. In addition, the energy cost of manufacturing microcapsules is an important factor to be considered when designing microcapsule systems and the corresponding production processes. Recent factors linked to UN sustainability goals are modifying how such microencapsulation systems should be designed in pursuit of "ideal" microcapsules that are efficient, safe, cost-effective and environmentally friendly. This review provides an overview of advances in microencapsulation, with emphasis on sustainable microcapsule designs. The key evaluation techniques to assess the biodegradability of microcapsules, in compliance with recently evolving European Union requirements, are also described. Moreover, the most common methodologies for the fabrication of microcapsules are presented within the framework of their energy demand. Recent promising microcapsule designs are also highlighted for their suitability toward meeting current design requirements and stringent regulations, tackling the ongoing challenges, limitations, and opportunities.

Commercial perfume microcapsules are becoming popular across the globe to fulfill consumers' demands. However, most of microcapsules rely on synthetic polymers and/or animal-sourced ingredients to form the shells. Therefore, replacement of the shell materials is imperative to minimize environmental microplastic pollution, as well as to meeting peoples' needs, religious beliefs, and lifestyles. Herein, we report a methodology to fabricate environmentally benign dual-shell (fungal chitosan-SiO₂) microcapsules laden with fragrance oil (hexyl salicylate). Anionically stabilized oil droplets were coated with fungal chitosan via interfacial electrostatic interactions at pH 2, which were then covered by an inorganic coating of SiO₂ produced via external alkaline mineralization of sodium silicate. Core-shell microcapsules with a spherical morphology were achieved. Under compression, dual-shell chitosan-SiO₂ microcapsules yielded a mean nominal rupture stress of 3.0 ± 0.2 MPa, which was significantly higher than that of single-shell microcapsules (1.7 ± 0.2 MPa). After 20 days in neutral pH water, only ∼2.5% of the oil was released from dual-shell microcapsules, while single-shell microcapsules cumulatively released more than 10%. These findings showed that the additional SiO₂ coating significantly enhanced both mechanical and barrier properties of microcapsules, which may be appealing for multiple commercial applications, including cosmetics and detergents.