Soutenance de thèse de LAGGOUNE Zohra
Titre de thèse
Conception et optimisation de procédés de traitement en milieu supercritique de dispositifs médicaux de cardiologie interventionnelle
Design and optimization of supercritical treatment processes for interventional cardiology medical devices
Résumé de la thèse
Atherosclerosis, characterized by arterial narrowing due to fatty deposits, is commonly treated with angioplasty using stents or balloons. Recent advances have led to active stents and balloons that release sirolimus through polymeric coatings to prevent restenosis. Conventional manufacturing methods of these devices using organic solvents may leave harmful residues.
This thesis explores supercritical CO2 technology as an eco-friendly alternative for producing and treating active coronary medical devices. The study first applied supercritical CO2 to extract residual solvent from active stents. Semi-continuous extraction at 8 MPa, 308.15 K for 0.5 h achieved 91.80 % of extraction yield while minimizing polymer detachment and maintaining satisfactory in-vitro sirolimus release.
The research also investigates supercritical impregnation of sirolimus for developing active balloons and stents. Balloon impregnation in batch mode at 18 MPa, 323.15 K for 18 h maximized drug loading to 0.68 µg.mm-2, while achieving positive ex-vivo results. In contrast, impregnations in batch mode of two types of stents (AMS® and HT Supreme®) resulted in low drug loadings and coating detachment. The development of the Fast Impregnation process significantly improved drug loadings from 0.035 to 1.11 µg.mm-2 for AMS®, and from 0.015 to 7.3 µg.mm-2 for HT Supreme®. This process preserved the coating integrity under conditions set at 12.5 MPa and 308.15 K for AMS®, and at 25 MPa and 313.15 K for HT Supreme®.
Thesis resume
Atherosclerosis, characterized by arterial narrowing due to fatty deposits, is commonly treated with angioplasty using stents or balloons. Recent advances have led to active stents and balloons that release sirolimus through polymeric coatings to prevent restenosis. Conventional manufacturing methods of these devices using organic solvents may leave harmful residues.
This thesis explores supercritical CO2 technology as an eco-friendly alternative for producing and treating active coronary medical devices. The study first applied supercritical CO2 to extract residual solvent from active stents. Semi-continuous extraction at 8 MPa, 308.15 K for 0.5 h achieved 91.80 % of extraction yield while minimizing polymer detachment and maintaining satisfactory in-vitro sirolimus release.
The research also investigates supercritical impregnation of sirolimus for developing active balloons and stents. Balloon impregnation in batch mode at 18 MPa, 323.15 K for 18 h maximized drug loading to 0.68 µg.mm-2, while achieving positive ex-vivo results. In contrast, impregnations in batch mode of two types of stents (AMS® and HT Supreme®) resulted in low drug loadings and coating detachment. The development of the Fast Impregnation process significantly improved drug loadings from 0.035 to 1.11 µg.mm-2 for AMS®, and from 0.015 to 7.3 µg.mm-2 for HT Supreme®. This process preserved the coating integrity under conditions set at 12.5 MPa and 308.15 K for AMS®, and at 25 MPa and 313.15 K for HT Supreme®.