Development of nanoparticles aggregates containing pharmaceuticals for application in regenerative medicine

• Autor(a) principal: Freitas, Bruno Filipe Gonçalves
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/25637
• topic: Biomedical Applications; Colloidal Gels; Drug delivery; Nanoparticles; Polymeric biomaterials

Chronic Inflammation and Musculoskeletal Diseases are two types of diseases with greater growth each year and already reaching a larger portions pf the population worldwide. The usual treatments, for both cases, are usually implicated in large periods of time and high associated costs. Therefore, the development of new materials that can be performed as a focal long-term drug delivery system is of great interest. In this context, the use of new pharmacological drugs through the use of natural products such as flavonoids (eg Quercetin and Naringin) appear as a promising approach. Quercetin is a flavonol naturally found in many fruits, legumes, leaves and granules and is exposed to antioxidant properties. Naringin is a naturally occurring flavone that occurs naturally in citrus fruits with bioactive in various bone disorders and may have promising in the boundary osteogenesis of stem cells. However, these flavonoids are typically hydrophobic and have low bioavailability because they are rapidly metabolized in vivo, which may limit their therapeutic use. The development of systems for drug delivery in a focused way is of great interest for a different plan of action. However the result of the operations is quite challenging and even the data are only visible were achieved In this context, this thesis focus on the development of two types of colloidal gels component compose of polymeric particles with efficient encapsulation of different types of flavonoids. For the encapsulation of Quercetin, a colloidal gel composed of anionic nanoparticles of Zein and hyaluronic acid (150.5 ± 0.7 nm) that were combine with PLGA coated in poly (ethylene) (PEI) as cationic nanoparticles (218.9 ± 2, 7 nm). These system present a high efficiency of Quercetin encapsulation (92 ± 1%) through the nanoprecipitation method. The Quercetin present in the colloidal gel had a controlled drug release profile relatively slow under physiological (pH =7 4) for the period of 20 days. The gel was afterwards put in macrophagic contact and its cytotoxicity was evaluated. The production of NO by the induction of inflammatory response by LPS and successive action of the gel with Quercetin was determined by the Method of Griess demonstrating a production of NO by macrophages. In order to improve the mechanical properties and to allow in situ fixation colloidal gels with a double crosslinking were also produced. The encapsulation of Naringin is a type of Zein nanoparticles methacrylated hyaluronic acid (155.9 ± 0.9 nm) with combinations of PLGA nanoparticles coated with poly (ethylenimine) methacrylate (PEIm) (229.7 ± 1.6 nm). This system demonstrated maximum efficiency of Naringin encapsulation (64 ± 7%) in Zein particles through the nanoprecipitation method. The release profile of the colloidal gel formed by UV crosslinking was compared to a colloidal gel formed by electrostatic crosslinking. Interestingly the methacrylated gel showed a slower release profile when compared to its predecessor. Subsequently for a pro-osteogenic consultation of this system the gel was placed in contact with human adipose tissue stem cells (ASCs). The results obtained demonstrate that the UV-crosslinked colloidal system has a greater expression of the enzyme alkaline phosphatase when compared to the pro-osteogenic or administration of enzymes in their free form. In general, double-crosslinked colloidal gels are a promising platform for the local delivery of flavonoids and demonstrate potential for the application of intelligent systems to different types of tissue damage.