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Porous and hybrid silica from biocompatible systems : application to drug release

Abstract : The objective of this work focuses on the preparation of porous, hybrid silicate materials doped with an active ingredient, based on biocompatible components for pharmaceutical applications, as drug delivery systems. The motivation for this study is related to the need to meet the growing demand for more effective drugs. The first point of interest of this study concerns the compounds used which are biocompatible, low-cost, and which are good candidates for the formation of mesostructured materials. The surfactant used was Kolliphor EL (KEL) and the oils were Miglyol 812N (Mig), and Isopropyl Myristate (IM). The active ingredient Ketoprofen (KTP) was chosen as the molecule model for the evaluation of release assays. Finally, HeLa cells, a cancer cell, were used to assess the toxicity of the synthesized materials. The first chapter is devoted to the state of the art of molecular structures based on non-ionic surfactants as KEL. Then, the main publications relating to porous and hybrid materials as drug carriers are summarized. At the end of this chapter, the kinetic release models and corresponding equations are presented. The second chapter brings together the methods and characterization techniques used. The third chapter studies the phase behaviour of the KEL/water binary system studied in this work and is described. The different 1- and 2-phase domains were determined and characterized by visual inspection, using polarized light optical microscopy and liquid crystal structures by SAXS. Then, the influence of oil addition in the KEL/water system was studied at 25°C. Ternary phase diagrams were established with Miglyol (Mig) and Isopropyl Myristate (IM). From these Mig and IM-based systems, mesoporous materials were prepared. With optimized synthesis conditions, the mesoporous network was structured in both cases. In the fourth chapter the influence of the addition of a block copolymer, the P123 in the KEL/water system is reported and the phase diagram is present. It evaluated the synergy of the two surfactants to form micelles and liquid crystals. Then, the effect of the addition of P123 micelles in Isopropyl Myristate based fine emulsions on the characteristics of the porous materials thus prepared using different P123 micelle contents, it is possible to vary the degree of porosity of the materials. For emulsion (Em)/micelle P123 proportions less than 50/50, mesoporous silicas with two pore sizes are obtained. When the Em/P123 ratio increases, it is possible to control the porosity of the materials. The fifth chapter concerns the study of the encapsulation of KTP in different systems and its release. Concentrated emulsions as well as hybrid materials based on micellar solutions and fine emulsions have been selected. Release studies were performed with a PbS solution at different pH levels: 7.4; 1.2 and 4.6. The results showed that, under neutral conditions, the KTP released by hybrid materials based on micellar solutions reaches 38% after 24 hours and the pH effect increases the amount of KTP released. Then, the release into a receptor solution with different concentrations of P123 was studied. The results show that the amount of KTP released in the presence of 5% P123, reach 65% after 24 hours. In the last part, the toxicity of doped materials and hybrid systems was assessed. The results show that the silica matrix protects the cells because cell viability is increased, from 64 to almost 80% with hybrid materials.
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Submitted on : Thursday, April 30, 2020 - 2:51:01 PM
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  • HAL Id : tel-02559524, version 1



Claudia Violeta Cervantes-Martinez. Porous and hybrid silica from biocompatible systems : application to drug release. Chemical Sciences. Université de Lorraine, 2019. English. ⟨NNT : 2019LORR0295⟩. ⟨tel-02559524⟩



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