Desenvolupament de gels lipídics avançats per aplicacions en pell i mucoses

Abstract

[cat] El desenvolupament de nous sistemes d’aplicació tòpica per millorar la salut en pell i mucoses esta experimentant un creixement significatiu. Aquests sistemes presenten l’avantatge de prescindir de l’administració oral de principis actius a altes concentracions, que sovint són necessàries per garantir l’eficàcia al lloc diana. D’aquesta manera, s’evita el metabolisme hepàtic, que pot estar associat amb efectes secundaris. Tot i que molts productes tòpics disponibles al mercat estan formulats amb ingredients no tòxics i biodegradables, sovint la seva biocompatibilitat és molt millorable. És a dir, els components de la formulació no són substàncies presents de manera intrínseca en el teixit de la pell o de les mucoses. Atès que l'anatomia i les característiques de cada tipus de teixit varien significativament, és essencial desenvolupar sistemes tòpics específics adaptats a les necessitats del teixit diana. Aquesta tesi té com a objectiu el desenvolupament, la caracterització i l’inici del procés d’industrialització de dos sistemes gel formats exclusivament per lípids i aigua. L'objectiu principal és dissenyar i caracteritzar aquests gels com a vehicles tòpics. Aquests materials han de ser capaços d’incorporar i alliberar molècules actives de manera eficient, amb l'objectiu final de millorar la salut de la pell i la mucosa.

[eng] The development of new topical delivery systems to improve skin and mucosal health is undergoing significant growth. These topical systems offer the advantage of avoiding oral administration of active ingredients at high concentrations, which are often required to ensure efficacy at the target site. Topical delivery systems avoid hepatic metabolism, which can be associated with side effects. Although many topical products on the market contain non-toxic and biodegradable ingredients, their components are not intrinsically present in the skin or mucosal tissues. Given the anatomical and physiological differences between each type of tissue, it is essential to develop specific topical systems adapted to the needs of the target tissue. This thesis focuses on the development, characterization, and initial steps toward industrialization of two gel-based systems composed exclusively of lipids and water. The primary objective is to design and characterize these gels as topical delivery vehicles, capable of efficiently incorporating and releasing active molecules, to improve both the skin and mucosa health. On the one hand, the industrialization process has commenced for a hydrogel composed of 5% lipids and 95% water without the need for crosslinking polymers or surfactants. This hydrogel exhibits thermoreversible properties, is stable and is composed of multilamellar lipid vesicles that interact with each other to form the three-dimensional network that constitutes the gel. This structure facilitates the encapsulation of both hydrophilic and lipophilic molecules. On the other hand, a bigel has been designed, combining 40% of the aforementioned hydrogel with 60% of an oleogel to obtain a highly stable biphasic microstructure that appears macroscopically homogeneous. Its composition — including lipid vesicles from the hydrogel, olive oil, and beeswax — allows the encapsulation of both hydrophilic and lipophilic molecules with high stability. Additionally, its rheological properties make it suitable for topical application. The skin and vaginal mucosa are physiologically distinct tissues. The stratum corneum of the skin acts as a barrier due to the presence of corneocytes and lipid lamellar structure, while the underlying epidermis exists in a more hydrated environment, consisting of stratified living cells in constant renewal. In contrast, the vaginal mucosa features a stratified epithelial layer in direct contact with the external environment, covered by vaginal fluid that maintains constant tissue hydration. The developed hydrogel and bigel are promising candidates for cutaneous application, as their interaction with stratum corneum lipids supports the transport of molecules into the different skin layers. For vaginal mucosal application, the lipidic hydrogel appears to be the most suitable candidate. Its composition is compatible with vaginal mucus, and it has demonstrated the ability to transport and retain active molecules within the mucosal epithelium. This study represents a significant step forward in the development of multifunctional, biocompatible systems for topical applications, offering safer and more effective solutions for skin and mucosa health care.