Philip Chennell

Reliable prediction of gas transport in polymeric materials requires accurate estimation of solubility and diffusion coefficients within dense, heterogeneous matrices. In this work, we systematically benchmark four molecular simulation approaches for solubility calculations, including free energy perturbation (FEP), Bennett acceptance ratio (BAR), thermodynamic integration (TI), and widom test-particle insertion (TPI), using a two-level strategy. First, methane hydration in water is employed as a stringent reference system to assess accuracy, convergence, and bias-variance behavior. Second, the validated methodologies are applied to gas solubility in amorphous isotactic polypropylene (iPP) for H2, O2, N2, and CO2 at 300 K. The different approaches provide broadly consistent estimates for methane hydration in water within the reported statistical uncertainties. In amorphous polypropylene, however, differences are observed between the finite-sampling insertion estimates and the alchemical free-energy results. These discrepancies highlight the challenges associated with adequate sampling of favorable insertion configurations in heterogeneous polymer environments and the need for careful convergence assessment. The resulting solubilities, expressed as Henry coefficients and corrected to an amorphous-phase basis, agree well with experimental data and reproduce the expected ordering CO2 > O2 ≳ N2 > H2. Diffusion coefficients obtained from mean-square displacement analysis follow the trend H2 > O2 ≳ N2 ≳ CO2 and exhibit Arrhenius temperature dependence over 250–400 K. Solubilities display linear van’t Hoff behavior with negative enthalpies of sorption, consistent with exothermic dissolution. These results provide a comparative assessment of molecular simulation approaches for gas solubility and offer insight into the thermodynamic and kinetic contributions governing gas transport in amorphous polyolefins.

The study of extractable chemicals is used to evaluate whether a medical device contains harmful substances susceptible to migrate and contaminate the patients they are used in. The analysis of the biomaterial itself after extraction is often left aside. The aim of this study is to characterise and investigate whether any changes occur during the extraction process. Two biomaterials (thermoplastic polyurethane (TPU) and silicone from intravenous catheters) were studied after extraction, using acetone and hexane. To study the surface, we used scanning electron microscopy (morphological aspect), energy dispersive spectroscopy and x-ray photoelectron spectroscopy (atomic composition), infrared spectroscopy (molecular composition). Thermogravimetric analysis and differential scanning calorimetry were used for in-depth characterisation. It was found that the extreme surface consisted of the polymer and external contaminants or organic products that had migrated from the core to the surface. Analysis of TPU showed that acetone was a suitable swelling agent. No significant change in the material was observed after hexane maceration. For silicone, the situation was reversed. We concluded that the solvents used were well suited for an extractables study of these two materials, and gained understanding of the phenomena that could lead to leaching during their medical use.

Les stents urétéraux et les sondes de néphrostomie sont constitués de silicone ou de polyuréthane thermoplastique (TPU). Afin de limiter les risques infectieux lors de leur implantation, une modification topographique par création de pores permettrait de limiter l’adhésion des bactéries et de former des réservoirs pour une libération in situ de substances antiinfectieuses. Ce travail vise à préparer des surfaces en polymère ayant un motif poreux tubulaire ordonné. Une réplication en deux temps à partir de surfaces ordonnées poreuses d’oxyde d’aluminium (PAAO) préparées par 2 méthodes (double anodisation douce et double anodisation dure/douce) a été mise en œuvre pour reproduire le motif initial sur des surfaces en silicone et TPU. Pour le moule intermédiaire trois matériaux ont été testés (acrylonitrile butadiène styrène, polystyrène et résine polyacrylate). Les surfaces ont toutes été caractérisées par des techniques microscopiques et spectroscopiques. Les surfaces en PAAO préparées par double anodisation douce possédaient des pores d’environ 50 nm de diamètre et 100 nm de profondeur, alors que celles obtenues après mise au point de la méthode dure/douce étaient de taille supérieure, d’environ 125 nm de diamètre et ayant des profondeurs de quelques centaines de nanomètres. La surface du moule intermédiaire est constituée de picots. Une adhésion latérale de ceux-ci a été observée pour certaines conditions. La meilleure réplication du motif a été obtenue pour le TPU. Les surfaces ainsi obtenues pourront être utilisées et optimisées lors de l'étude ultérieure de l'adhésion du biofilm.

Drug losses during infusions can be caused by complex adsorption and absorption phenomena at the interface between aqueous formulations and polymer-based medical devices, most commonly made of plasticized poly(vinyl chloride) (PVC). Despite their success in describing adsorption phenomena, molecular simulation methods are inherently limited by their length and time scales, which precludes their application to the study of absorption processes. Here, we extended this molecular understanding using the Martini 3 coarse-grained framework to explore absorption within plasticized PVC matrices containing either DEHT or TOTM plasticizers. We used a top-down approach to refine intermolecular interactions. After optimizing the solute-water and solute-PVC nonbonded interactions to reproduce experimental partitioning data, we combined potential of mean force (PMF), free-energy perturbation (BAR), and long equilibrium simulations to map both the thermodynamic and kinetic aspects of sorption. This work establishes a transferable coarse-grained framework for modeling drug-polymer interactions over extended time scales, bridging atomistic insights with experimental observations and paving the way toward full infusion-system simulations including excipients and complex polymer formulations.

Short contacts between medical devices and medications that they contain can cause drug sorption or leaching of unwanted compounds which can have clinical consequences. However, the parameters that govern these interactions are still incompletely understood. The objectives of this study were to evaluate the impact of the formulation parameters on migration of 2,4 Di-tert-butylphenol (2,4 DTBP) and sorption of tacrolimus (TAC) in a model micellar ophthalmic drug formulation which is known to interact with silicone elastomers. A design of experiments was established to evaluate the impact of the formulation parameters on 2,4 DTBP leaching and tacrolimus sorption by varying the initial concentrations of TAC (0.04; 0.2 and 1 mg/mL), polyoxyethylenated castor oil (KEL) (32; 80 and 200 mg/mL) and ethanol absolute (EtOH) (10 and 100 mg/mL), at 5°C and 25°C, during static contact between various formulations and silicone valves obtained from an ophthalmic multidose delivery device. Concentrations of 2,4 DTBP and TAC were monitored by liquid chromatography coupled with an UV–visible detector. Under the conditions studied, the amount of 2,4 DTBP leaching out increased during contact with the silicone valve, with increasing TAC concentration being quite interestingly the main factor decreasing its ability to leach out, whilst ethanol increased its leachability. The silicone valve did not cause any significant decrease of TAC concentrations over the duration of the study, regardless of the concentrations of KEL, EtOH, or temperature. This study showed the impact of formulation on the leaching of 2,4 DTBP from a silicone component. Graphical Abstract

Bone infections are common and difficult to treat, and secondary bone defects, which are often observed, may require a bone allograft. In this case, the surgeon will add antibiotics (usually vancomycin) in direct contact with the bone graft during the procedure, in order to allow in-situ release after implantation in the operating site. Dalbavancin is a novel antibiotic indicated for treating acute bacterial infections resistant to vancomycin. Its modified chemical structure grants it an increased half-life that could modify its release kinetics from the bone allograft. The aim of this study was to determine the release kinetics of dalbavancin from bone grafts after they were immersed in a dalbavancin solution. The study was conducted using a Design of Experiments (DoE) protocol. Decellularized and delipidated allograft bone cubes were preliminarily characterized and put into contact with dalbavancin solutions. The parameters that were studied where the allograft mass, initial dalbavancin concentration and contact time. The samples were then transferred into the release media, which was sampled over time and dalbavancin was quantified using a high pressure liquid chromatography with diode array detector method that was developed for the occasion. Our results showed that on average, dalbavancin was fully released after 5 min for the lower mass bone grafts, but after 60 min for the high mass and high concentration conditions. Contact time had no impact, thus indicating a fast loading process of dalbavancin into the allograft. Although our study revealed the possible benefits of using dalbavancin in bone grafting, an in-vivo study is required to confirm our hypotheses. Graphical Abstract

Insulin aspart, a biomacromolecule essential for diabetes treatment, is known to interact with polymer-based drug delivery systems. Plasticized poly(vinyl chloride) (PVC) materials, widely used in medical infusion tubing, contribute significantly to insulin aspart loss due to adsorption. However, experimental studies alone cannot distinguish the individual contributions of plasticizers and the PVC matrix in this process. To address this, we employed coarse-grained molecular dynamics (Martini 3) simulations to investigate protein-surface interactions over extended time scales, providing deeper insights into adsorption mechanisms. Our results revealed a strong preference for insulin aspart adsorption onto PVC regions rather than plasticizers, explaining the experimentally observed lack of adsorption differences between plasticized and nonplasticized PVC surfaces. Additionally, we explored the formation of the insulin aspart adsorption layer for both monomeric and hexameric forms, further characterizing the thermodynamics of the adsorption process.