Medical devices can be contaminated by microbial biofilm which causes nosocomial infections. One of the strategies for the prevention of such microbial adhesion is to modify the biomaterials by creating micro or nanofeatures on their surface. This study aimed (1) to nanostructure acrylonitrile-butadiene-styrene (ABS), a polymer composing connectors in perfusion devices, using Anodic Alumina Oxide templates, and to control the reproducibility of this process; (2) to characterize the physico-chemical properties of the nanostructured surfaces such as wettability using captive-bubble contact angle measurement technique; (3) to test the impact of nanostructures on Staphylococcus epidermidis biofilm development. Fabrication of Anodic Alumina Oxide molds was realized by double anodization in oxalic acid. This process was reproducible. The obtained molds present hexagonally arranged 50 nm diameter pores, with a 100 nm interpore distance and a length of 100 nm. Acrylonitrile-butadiene-styrene nanostructures were successfully prepared using a polymer solution and two melt wetting methods. For all methods, the nanopicots were obtained but inside each sample their length was different. One method was selected essentially for industrial purposes and for better reproducibility results. The flat ABS surface presents a slightly hydrophilic character, which remains roughly unchanged after nanostructuration, the increasing apparent wettability observed in that case being explained by roughness effects. Also, the nanostructuration of the polymer surface does not induce any significant effect on Staphylococcus epidermidis adhesion.

Plasticizers added to polyvinylchloride (PVC) used in medical devices can be released into patients’ biological fluids. Di-(2-ethylhexyl)phthalate (DEHP), a well-known reprotoxic and endocrine disruptor, must be replaced by alternative compounds. Di-(2-ethylhexyl) terephthalate (DEHT) is an interesting candidate due to its lower migration from PVC and its lack of reprotoxicity. However, there is still a lack of data to support the safety of its human metabolites with regard to their hormonal properties in the thyroid system. The effects of DEHT metabolites on thyroid/hormone receptors (TRs) were compared in vitro and in silico to those of DEHP. The oxidized metabolites of DEHT had no effect on T3 receptors whereas 5-hydroxy-mono-(ethylhexyl)phthalate (5-OH-MEHP) appeared to be primarily an agonist for TRs above 0.2 µg/mL with a synergistic effect on T3. Monoesters (MEHP and mono-(2-ethylhexyl)terephthalate, MEHT) were also active on T3 receptors. In vitro, MEHP was a partial agonist between 10 and 20 µg/mL. MEHT was an antagonist at non-cytotoxic concentrations (2–5 µg/mL) in a concentration-dependent manner. The results obtained with docking were consistent with those of the T-screen and provide additional information on the preferential affinity of monoesters and 5-OH-MEHP for TRs. This study highlights a lack of interactions between oxidized metabolites and TRs, confirming the interest of DEHT.

Background: ECMO is a therapeutic act with a high risk of exposure to diethylhexylphthalate (DEHP), plasticizer from PVC tubings. The replacement of this plasticizer with alternative compounds is recommended but the risks associated with the use of new plasticizers have not been evaluated in ECMO situations. Methods: Ex vivo ECMO models were performed with different flow rates over 6 days to evaluate the migration of plasticizers and their potential toxic risk for patient. The release of plasticizers during ECMO was measured and compared to reference value (derived no effect level, DNEL) and to cytotoxic concentration carried out with MTT test. Results: Trioctyltrimellitate (TOTM), main plasticizer present in circuit (44% w/w), is weakly released during ECMO. Concentrations are not cytotoxic and exposure doses are lower than DNEL. In contrast, DEHP doses are higher than the DNEL despite a lower presence of DEHP in the circuit (0.2%). We have shown that DEHP is not coming from the circuit but from the priming bag. Replacing this bag with a multilayer one avoids the exposure to DEHP. Conclusion: Our study shows that circuits made of PVC plasticized with TOTM against DEHP improves the safety of ECMO.

Tacrolimus is an immunosuppressant used to treat a large variety of inflammatory or immunity-mediated ophthalmic diseases. However, there are currently no commercial industrial forms available that can provide relief to patients. Various ophthalmic formulations have been reported in the literature, but their stability has only been tested over short periods. The objective of this study was to evaluate the physicochemical stability of a preservative-free tacrolimus formulation (0.2 and 1 mg/mL) at three storage temperatures (5 °C, 25 °C and 35 °C) for up to nine months in a multidose eyedropper. Analyses performed were the following: visual inspection and chromaticity, turbidity, viscosity, size of micelles, osmolality and pH measurements, tacrolimus quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, tacrolimus quantification was also performed on the drops emitted from the eyedroppers. All tested parameters remained stable during the nine month period when the eyedrops were stored at 5 °C. However, during storage at 25 °C and 35 °C, several signs of chemical instability were detected. Furthermore, a leachable compound originating from a silicone part of the eyedropper was detected during the in-use assay. Overall, the 0.2 mg/mL and 1 mg/mL tacrolimus ophthalmic solutions were physicochemically stable for up to nine months when stored at 5 °C.

Care management of newborns in the neonatal intensive care unit (NICU) requires numerous PVC (PolyVinyl Chloride) medical devices (MD) containing plasticizers that can migrate and contaminate the patient. We measured the magnitude of neonates’ exposure to plasticizers (di-ethylhexylphthalate (DEHP) and alternatives) in relation to urinary concentrations of their metabolites. Plasticizers’ exposure was evaluated (1) by calculating the amounts of plasticizers prone to be released from each MD used for care management, and (2) by measuring the patients’ urinary levels of each plasticizers’ metabolites. 104 neonates were enrolled. They were exposed to di-isononylphthalate (DINP), especially via transfusion and infusion MD, and to DEHP via ECMO (Extra Corporeal Membrane Oxygenation) and respiratory assistance MD. Mean exposure doses exceeded the derived no-effect level of DINP and DEHP by a 10-fold and a 1000-fold factor. No PVC MD were plasticized with di-isononylcyclohexane-1,2-dicarboxylate (DINCH). High urinary concentrations of DEHP metabolites were directly correlated with DEHP exposure through ECMO MD. Urinary concentrations of DINP metabolites in transfused patients were also high. DINCH metabolites were found in urine, suggesting another route of exposure. Neonates in NICU are considerably exposed to plasticizers, with magnitudes varying with the type of MD used. The high exposure to DEHP and DINP leads to a risk of their metabolites’ toxicity.