My assigned project under the supervision of Dr. Anna Roig and Dr. Concepción Domingo was focused on the preparation of multifunctional silica-based nanoparticles for biomedical applications. The thesis aims to fabricate hybrid (organic-inorganic) complex materials as drug carriers using supercritical fluids (SCFs) with adequate properties for their application in biomedicine. For that purpose, two main objectives have been addressed: first, evaluation of the potentiality of porous silica-based materials synthesized without using porogenic agents as drug delivery systems; and second, exploiting the utility of the supercritical fluids in the synthesis and functionalization of materials. During the realization of this thesis, silica-based nanostructured materials have been synthesized, loaded with a model drug, physical and chemically modified in their surface, and preliminarily studied as potential biomedical tools analyzing their interactions with relevant biological entities and media. The manuscript is organized into eight chapters. • Chapter 1 provides a general introduction to nanotechnology and colloidal science (with a special mention to nanomedicine) together with the main strategies to synthesize both silica and iron oxide nanoparticles and their biomedical applications. A brief explanation on magnetism is also given, as well as descriptions and uses of SCFs in materials science. The aim of the chapter is to place the reader in the scientific context of the thesis. • Chapter 2 describes the synthesis and characterization of the porous silica-based materials employed in the thesis: silica monolithic aerogels, silica submicron-sized particles and composite core(iron oxide)-shell(silica) nanoparticles. • Chapter 3 reports on the fabrication of hybrid products for biomedical applications by impregnating silica-based materials with a therapeutic agent trough dissolution in supercritical carbon dioxide. The chapter includes the simultaneous in situ preparation and encapsulation of two organic photosensitizers as a proof-of-concept. Details on the processes and on the characterization, in terms of organic load, structural and textural properties of the resulting materials, are presented. Special attention is devoted to the chemical conformation and stability of the drug inside the silica matrices and to the in vitro release kinetics in aqueous media. • Chapter 4 explains the use of biopolymers to coat the silica-based particles conferring them with enhanced properties for biomedical uses, such as sustain drug release and improved features for the interactions with cells. Coating method involved the use of compressed carbon dioxide as antisolvent or as reaction medium and catalyst for the polymer. The morphological properties and thermal stability of the resulting materials are presented. Results on In vitro drug delivery in aqueous media and drug stability are presented and compared with those found for uncoated particles. • Chapter 5 shows preliminary studies of our materials as potential drug carriers, in terms of degradability, colloidal stability in biological media, cytotoxicity and cellular uptake. Strategies of silica surface functionalization with the goal of overcoming problems encounter in bioapplications are also gathered. • Chapter 6 lists the general conclusions derived from the present thesis and includes some suggestions for further research on the topic. • Chapter 7 gives brief introductions to the theoretical fundaments of the used experimental techniques and technical characteristics of the employed equipments. • Chapter 8 contains information about the author and the publications obtained during the PhD work.
|Date of Award||14 Nov 2014|
|Supervisor||Anna Roig Serra (Director), Maria Concepción Domingo Pascual (Director) & Jose Antonio Ayllon Esteve (Tutor)|