Pazos Medina, María del Carmen Matos González, María
Ingeniería Química y Tecnología del Medio Ambiente, Departamento de
Ingeniería de procesos y ambiental Química de coloides Dispersiones Absorción de los fármacos Antioxidantes en los alimentos
The main objective of this thesis is the preparation of vesicles formed by the self-assembly of non-ionic surfactants (niosomes) of interest in food, pharmaceutical and cosmetic industries, containing trans-resveratrol (RSV), a bioactive compound with antioxidant capacity and beneficial effects for human health. First, the suitability of niosomes to encapsulate RSV was studied using Span 80 and Span 60 as surfactants, and cholesterol as membrane stabilizer. Niosomes were prepared by a two-stage technique: mechanical agitation followed by sonication. The niosomal formulations were evaluated in terms of their morphology, mean size, size distribution, stability, entrapment efficiency (EE), and in vitro RSV release. High speed mechanical agitation produced niosomes with smaller mean size, narrower size distribution, and lower EE values. Mean size, stability and EE of the niosomes were affected not only by their composition, but also by the protocol used in their preparation. Taking into consideration the importance of vesicular systems as nanocarriers in dermal and transdermal delivery, RSV was incorporated into niosomes and liposomes and its ex-vivo percutaneous absorption in newborn pig skin was investigated using Franz diffusion cells. Cholesterol was also added as membrane stabilizer. The influence of vesicle composition on its physicochemical properties and stability was evaluated. Phosphatidylcholine was used in liposomes formulation while niosomes were formulated with two suitable skin-compatible oleins commonly used in pharmaceutical formulations as surfactants. The results obtained in this work enabled us to confirm that niosomes are more suitable than liposomes as carriers for percutaneous absorption of RSV. Then, nanodesign of RSV entrapped niosomes for oral administration using food-grade surfactants and dodecanol as membrane stabilizer was carried out. RSV entrapped niosomes were prepared using a modified thin film hydration method, and their suitability as yoghurt additive was studied. Dodecanol was selected as a membrane stabilizer to avoid potential adverse health effects of cholesterol, as well as the rejection by the consumer of this functional food. A factorial design of experiments was carried out to reduce the number of experiments, and an analysis of variance (ANOVA) was used to optimize the key parameters involved in niosome preparation. The addition of niosomes containing RSV did not involve changes in the textural properties of regular yoghurt. Finally, a new approach to formulate RSV entrapped niosomes for topical applications was proposed, and two specific preparation methods were applied and compared: thin film hydration and sonication method (TFH-S) with minor modifications, and ethanol injection modified method (EIM). Niosomes were formulated using Gelot 64 (G64) as surfactant and two suitable skin-compatible unsaturated fatty acids, commonly used in pharmaceutical formulations: oleic acid (OA) and linoleic acid (LA) as penetration enhancers. The EIM method allowed obtaining niosomes with smaller mean size, narrower size distribution and higher EE values than those provided by the TFH-S method.
Tesis con mención internacional. Tesis doctoral por el sistema de compendio de publicaciones