Couches minces nanocomposites contrôlées pour un nouveau système d'administration de médicaments pour des implants cardiovasculaires : décomposition des précurseurs organiques et transport des nanoparticules dans un plasma de décharge à barrière diélectrique à pression atmosphérique

Diseases of the heart and blood vessels are still the leading causes of death in most European countries, as well as Canada and the USA. Often, a blockage of the arteries induced by stenosis results in the need for a bypass surgery. Even though, harvesting the vein from the patient himself, avoiding immune response, seems like the most advantageous solution, it does in fact, in one third of the cases, show to be unsuccessful. For that reason, polytetrafluoroethylene (PTFE) vascular grafts are used. They show to have good mechanical properties and stability but could, in some cases, have unwanted side effect and cause neointimal hyperplasia on the interface between the native vessel and the vascular graft, this in return can result in restenosis. In order to inhibit this phenomenon, it has been proposed to use a drug, imatinib mesylate (IM), which is an inhibitor of three kinase receptors: PDGF-R, c-Kit and abl, where the first two ones are implicated in the occurrence of neointimal hyperplasia. It has been shown that small doses of IM successfully inhibit SMC proliferation without slowing down the endothelialisation, hence it has been chosen as the drug to improve the functionality of PTFE vascular grafts.The goal of this project was to find a way to develop an innovative approach to incorporate imatinib mesylate into the vascular grafts and enable its controlled release upon contact with the blood. To do that, the creation of thin films by Atmospheric Pressure Plasma Enhanced Chemical Vapor Deposition (AP-PECVD) in a Dielectric Barrier Discharge (DBD) configuration was chosen to be conducted. However, to protect the drug from the energetic and reactive plasma species, nanoparticles (NPs) were used to encapsulate the drug and to act as another level for controlled drug release. Indeed, deposition of an organic nanostructured, by silica nanoparticles, drug-filled thin layer has been achieved under atmospheric pressure in an argon plasma. The way this problem was tackled, was to first study the behavior of the organic precursor in the plasma by in-situ Fourier Transform Infrared Spectroscopy (FTIR), while the thin film is deposited and compare with the characterization of the final layer. First, the observation of artefacts in infrared spectra of plasmas, mistakenly attributed in the literature to vibration lines, was explained and described mathematically. The results obtained show that the wavenumber at which these artefacts are observed depends on the frequency at which the plasma is generated and on the sampling frequency of the interferogram measured by the spectrometer. Secondly, plasma technology at atmospheric pressure in FSK (Frequency Shift Keying) mode at 1 kHz and 15 kHz was used to simultaneously deposit a plasma polymer, using ethyl lactate as a precursor, and silica nanoparticles, dispersed beforehand in the precursor. This work clearly shows that the nanoparticles are preferentially deposited during the low frequency cycle of the discharge, while the polymerization of the precursor, which requires more energy, is rather observed at a higher frequency. Subsequently, space-resolved infrared spectroscopy was used to compare the polymerization mechanisms of ethyl lactate for two modes of discharge, namely the filamentary regime and the homogeneous regime. The results thus generated made it possible to follow the degradation of the organic precursor throughout the discharge and to correlate this information with the composition of the plasma polymer deposited. They also showed that FTIR gas spectroscopy makes it possible to characterize the NPs. Finally, the conclusions of this thesis present preliminary results which aim to demonstrate the feasibility of applying the developed layers to vascular prostheses and the potential of the overall strategy to inhibit the proliferation of smooth muscle cells.

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