Marc Bria

Programmable Polymer‐Based Supramolecular Temperature Sensor with a Memory Function

A new class of polymeric thermometers with a memory function is reported that is based on the supramolecular host-guest interactions of poly(N-isopropylacrylamide) (PNIPAM) with side-chain naphthalene guest moieties and the tetracationic macrocycle cyclobis(paraquat-p-phenylene) (CBPQT(4+)) as the host. This supramolecular thermometer exhibits a memory function for the thermal history of the solution, which arises from the large hysteresis of the thermoresponsive LCST phase transition (LCST = lower critical solution temperature). This hysteresis is based on the formation of a metastable soluble state that consists of the PNIPAM-CBPQT(4+) host-guest complex. When heated above the transition temperature, the polymer collapses, and the host-guest interactions are disrupted, making the polymer more hydrophobic and less soluble in water. Aside from providing fundamental insights into the kinetic control of supramolecular assemblies, the developed thermometer with a memory function might find use in applications spanning the physical and biological sciences.

DNA modification by oxovanadium(IV) complexes of salen derivatives

AbstractOxovanadium(IV) complexes of hydroxysalen derivatives have been prepared and tested as DNA reactive agents. The nuclease activity has been investigated under oxidative or reducing conditions, on the basis of the various oxidation states of vanadium: VIII, VIV and VV. In the absence of an activating agent, none of the compounds tested was able to induce cleavage of DNA, whereas in the presence of mercaptopropionic acid (MPA) or Oxone the four complexes induced DNA modifications. Under both conditions, the para-hydroxy complex was found to be the most active compound. Reaction of these salen complexes with DNA occurs essentially at guanine residues and is more efficient in the presence of Oxone than under reducing conditions. The extent of Oxone-mediated DNA oxidation by the four vanadyl complexes was clearly superior to VOSO4 and was observed without piperidine treatment. EPR studies provided information on the reactive metal-oxo species involved under each conditions and a mechanism of reaction with DNA is discussed.

Multilayered textile coating based on a β-cyclodextrin polyelectrolyte for the controlled release of drugs

The aim of this work was to develop the formation of multilayered coating incorporating a cyclodextrin polyelectrolyte onto a non-woven polyethylene terephthalate (PET) textile support in order to obtain reservoir and sustained release properties towards bioactive molecules. We optimized the multilayer assembly immobilization onto the PET surface according to the layer-by-layer (LbL) deposition process. After a pre-treatment of the textile support aiming to offer a sufficient ionic character to the surface, it was alternatively immersed into two polyelectrolytes aqueous solutions consisting of chitosan (CHT) as polycation on the one hand, and a β-cyclodextrin polymer (polyCTR-βCD) as polyanion on the other hand. In a second approach, a TBBA/polyCTR-βCD complex (4-tert-butylbenzoic acid, TBBA) was used in order to load the system with a drug model whose kinetics of release was assessed. Gravimetry, microscopy, OWLS, colorimetric titration, infrared and zetametry were used as characterization techniques. An effective deposition on the textile surface due to ionic interactions with alternation of up to 10 layers of each of both polyelectrolytes was clearly evidenced. However, we observed that layer formation occurred to a lesser extent when TBBA/polyCTR-βCD complex was applied instead of polyCTR-βCD alone. The release study showed that drug reservoir properties and release kinetics could be controlled by the number of layers in the system and that TBBA release was faster than the multilayered coating degradation.

Methyl-β-cyclodextrin modified vascular prosthesis: Influence of the modification level on the drug delivery properties in different media

A textile polyester vascular graft was modified with methyl-β-cyclodextrin (MeβCD) to obtain a new implant capable of releasing antibiotics directly in situ at the site of operation over a prolonged period and thereby prevent post-operative infections. We investigated the influence of the curing parameters (time and temperature) that allow control of the degree of functionalization (DF) of the support by MeβCD. The inclusion of ciprofloxacin (CFX) in the MeβCD cavity was observed in solution by two-dimensional (1)H NMR spectroscopy. The amount of CFX loaded on the modified graft increased with DF. Depending on the release medium (water, phosphate-buffered saline, or human plasma) and the DF of the prostheses, different kinetic profiles of release of CFX were obtained. The sustained release of CFX in human plasma was shown by microbiological assays that indicated prolonged antimicrobial activity against Staphylococcus aureus and Escherichia coli. Viability tests demonstrated the non-toxicity of MeβCD to an epithelial cell line (HPMEC), although a decrease in endothelial cell number was observed on the functionalized prosthesis, probably due to the roughness of the coating and also to the nature of the MeβCD polymer present on the surface of the fibers.

Comparative study of vascular prostheses coated with polycyclodextrins for controlled ciprofloxacin release

A textile polyester vascular graft was modified with cyclodextrins to obtain a new implant capable of releasing antibiotics (here ciprofloxacin, CFX) over prolonged time periods and thereby reducing the risk of post-operative infections. In this study, we compared samples modified with native and modified cyclodextrins, presenting different cavity sizes (β or γ cyclodextrins) and different substituent groups (hydroxypropyl and methyl). Drug release was measured in water, phosphate buffer pH 7.4 and blood plasma. The inclusion of CFX in the cyclodextrins cavities was observed in solution by two-dimensional (1)H NMR spectroscopy and confirmed by (1)F NMR measurements. Grafts modification with all cyclodextrins induced an increase of their sorption capacity towards CFX whose extent depended on the nature of the cyclodextrin: a 4-fold and 10-fold increase was observed in the cases of hydroxypropyl cyclodextrins and methylated β-cyclodextrin, respectively. Depending on the type of release medium and nature of CD, different CFX release kinetics were obtained. The discussion highlighted not only the role of the host guest complexation, but also that of the electrostatic interactions that occur between the anionic crosslinks of the cyclodextrins polymers, and CFX that presents a zwitterionic character. The microbiological assessment confirmed sustained CFX release in human plasma and demonstrated antibacterial efficiency of CD modified prostheses against Staphylococcus aureus and Escherichia coli for at least 24 h (compared to 4 h in the case of virgin grafts).

LCST: a powerful tool to control complexation between a dialkoxynaphthalene-functionalised poly(N-isopropylacrylamide) and CBPQT4+ in water

We describe the application of the LCST of a naphthalene-functionalised polyNIPAM derivative as a convenient, tuneable and reversible method to disrupt complex formation with CBPQT(4+) in water.

Translational Diffusion in Mixtures of Imidazolium ILs with Polar Aprotic Molecular Solvents

Self-diffusion coefficients of cations and solvent molecules were determined with (1)H NMR in mixtures of 1-n-butyl-3-methylimidazolium (Bmim(+)) tetrafluoroborate (BF4(-)), hexafluorophosphate (PF6(-)), trifluoromethanesulfonate (TfO(-)), and bis(trifluoromethylsulfonyl)imide (TFSI(-)) with acetonitrile (AN), γ-butyrolactone (γ-BL), and propylene carbonate (PC) over the entire composition range at 300 K. The relative diffusivities of solvent molecules to cations as a function of concentration were found to depend on the solvent but not on the anion (i.e., IL). In all cases the values exhibit a plateau at low IL content (x(IL) < 0.2) and then increase steeply (AN), moderately (γ-BL), or negligibly (PC) at higher IL concentrations. This behavior was related to the different solvation patterns in the employed solvents. In BmimPF6-based systems, anionic diffusivities were followed via (31)P nuclei and found to be higher than the corresponding cation values in IL-poor systems and lower in the IL-rich region. The inversion point of relative ionic diffusivities was found around equimolar composition and does not depend on the solvent. At this point, a distinct change in the ion-diffusion mechanism appears to take place.

Multi-stimuli responsive supramolecular diblock copolymers

A well-defined cyclobis(paraquat-p-phenylene) (CBPQT4+) end-functionalized poly(n-butyl acrylate) 3 was prepared via RAFT polymerization using a new trithiocarbonate CBPQT4+ derivative 2 as a reversible chain transfer agent. We have shown that the electron-poor CBPQT4+ moiety at the α-chain-end could be specifically modified by complex formation with various functionalized macromolecules featuring complementary electron rich end groups, thereby leading to the corresponding supramolecular diblock copolymers. The latter could be conveniently disassembled upon heating, by applying electrochemical redox processes or by the addition of a competing molecular guest. Furthermore, we can generate new diblock architectures upon the addition of an appropriately functionalized polymer. We also describe preliminarily results regarding the formation of nanostructured architectures both in solution and in thin films.

Visceral mesh modified with cyclodextrin for the local sustained delivery of ropivacaine

The aim of the study was to develop a polyester visceral implant modified with a cyclodextrin polymer for the local and prolonged delivery of ropivacaine to reduce post operatory pain. Therefore, we applied a coating of an inguinal mesh with a crosslinked polymer of hydroxypropyl-β-cyclodextrin (HPβCD) whose specific host-guest complex forming properties were expected to improve the adsorption capacity of the implant toward anesthetic, and then to release it within a sustained period. The modification reaction of the textile with cyclodextrin was explored through the study of the influence of the pad/dry/cure process parameters and the resulting implant (PET-CD) was characterized by solid state NMR and SEM. Besides, the inclusion complex between ropivacaine and CD was studied by NMR and capillary electrophoresis in PBS medium. Finally, ropivacaine sorption test showed that a maximum of 30 mg/g of ropivacaine could be adsorbed on the functionalized samples. In dynamic batch tests in PBS at pH 7.4, the release could be observed up to 6h. The cytocompatibility of the PET-CD loaded with ropivacaine was also studied and reached 65% cell vitality after 6 days.

Elaboration of Thermoresponsive Supramolecular Diblock Copolymers in Water from Complementary CBPQT4+ and TTF End‐Functionalized Polymers

A well-defined poly(N-isopropyl acrylamide) 1 incorporating at one termini a cyclobis(paraquat-p-phenylene) (CBPQT(4+)) recognition unit is prepared via a RAFT polymerization followed by a copper-catalyzed azide-alkyne cycloaddition (CuAAC). (1)H NMR (1D, DOSY), UV-vis and ITC experiments reveal that polymer 1 is able of forming effective host-guest complexes with tetrathiafulvalene (TTF) end-functionalized polymers in water, thereby leading to the formation of non-covalently-linked double-hydrophilic block copolymers. The effect of the temperature on both the LCST phase transition of 1 and its complexes and on CBPQT(4+)/TTF host-guest interactions is investigated.