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- Miméticos do “glucagon-like peptide-1” (GLP-1) e o seu potencial farmacêutico no controlo da diabetes tipo 2 e da obesidadePublication . Andreani, Tatiana; Souto, Eliana B.; Silva, Amélia M.; Lopes, Carla MartinsA diabetes mellitus do tipo 2 é caracterizada pela resistência à insulina e pela disfunção das células β do pâncreas. Os péptidos gastrintestinais, “gastric inhibitory polypeptide” (GIP) e “glucagon-like peptide-1” (GLP-1), são hormonas incretinas que estimulam, maioritariamente, a produção de insulina pós-prandial. Formulações contendo GLP-1 possuem um grande potencial no tratamento desta doença. Porém, o GLP-1 é eficaz apenas quando administrado por via parentérica. Para o tratamento da diabetes mellitus tipo 2 são usados análogos do GLP‑ 1 ou miméticos da incretina os quais são eficazes por via subcutânea. The pathogenesis of diabetes mellitus type 2 includes insulin resistance and progressive β-cell dysfunction. The gastrointestinal peptides, gastric inhibitory polypeptide (GIP) and glucagon‑like peptide-1 (GLP-1), are incretin hormones which are responsible for the major part of postprandial insulin secretion. Formulations containing GLP-1 have a great potential in the treatment of diabetes mellitus type 2. Nonetheless, GLP-1 is only efficient by continuous parenteral administration. GLP-1 analogues or incretin mimetics, exendine-4, are active after subcutaneous injection and can be used in the treatment of diabetes mellitus of type 2.
- Risperidone release from solid lipid nanoparticles (SLN): validated HPLC method and modelling kinetic profilePublication . Silva, Ana Catarina; Lopes, Carla Martins; Fonseca, J.; Soares, M.E.; Santos, D.; Souto, Eliana B.; Ferreira, D.A simple reverse-phase (RP) high performance liquid chromatography (HPLC) method was developed and validated, according to the International Harmonisation Guidelines (ICH), for the determination of risperidone (RISP) from solid lipid nanoparticles (SLN). Chromatographic runs were performed on a RP-C18 column, using an isocratic mobile phase of methanol, acetate buffer (0.05 M; pH 4.6) and triethylamine (60:40:0.02, v/v/v). The flow rate was 1 ml/min, the run time was 10 min and the RISP absorbance was measured at 280 nm, using UV detection. A linear response was obtained for a RISP concentration range of 0.25 - 10.00 g/ml (R2 = 0.9996), with a detection and quantification limits of 0.011 and 0.034 g/ml, respectively. The method was shown to be specific, precise at the intra-day (RSD < 0.796%) and inter-day (RSD < 0.331%) levels, and accurate with recoveries between 86.86 - 100.3% (RSD < 0.613%). Method robustness was observed as well. The suitability of the method for RISP quantifications was assessed by the determination of encapsulation parameters (encapsulation efficiency and drug loading) and by studying the RISP release profile from SLN. Kinetic models (zero order, Higuchi, Korsmeyer-Peppas and Baker-Lonsdale) were used to fit the obtained release profile and to predict the in vivo performance of RISP-loaded SLN. A combined pattern of diffusion and erosion release mechanism (anomalous non-Fickian transport) was found for the RISP-loaded SLN, which shows the ability of the system for controlled drug release.
- Novos sistemas terapêuticos nanotecnológicosPublication . Marques, Inês; Lopes, Carla Martins; Souto, Eliana B.A Nanotecnologia é uma nova ciência que emergiu nos últimos anos em várias áreas de aplicação, incluindo a da actividade farmacêutica, em particular na concepção de novas formas farmacêuticas. Com efeito, a produção de novas formas farmacêuticas constituídas por nanocristais de fármacos tem vindo a adquirir cada vez mais interesse por parte da comunidade científica. A principal vantagem da utilização de nanocristais de fármacos está directamente relacionada com a facilidade inerente ao processo de produção. O objectivo final consiste na produção de uma suspensão de partículas de fármaco com dimensões inferiores a 1 μm, que seja física e quimicamente estável, garantindo a viabilidade tecnológica e terapêutica para um determinado fármaco. Nanotechnology is a novel science which has emerged in the latest years in several fields, including the pharmaceutical sciences in particular in the development of novel drug delivery systems. Among the scientific community, the production of drug nanocrystals as novel delivery systems has being gathering attention. The main advantage of drug nanocrystals includes production facilities available. The final aim of this technology is to produce a physicochemically stable suspension to warrantee technological and therapeutic feasibility for a particular drug.
- Nanoparticulate carriers (NPC) for oral pharmaceutics and nutraceuticsPublication . Lopes, Carla Martins; Martins-Lopes, P.; Souto, Eliana B.The introduction of nanoparticulate carriers (NPC) in the pharmaceutic and nutraceutic fields has changed the definitions of disease management and treatment, diagnosis, as well as the supply food chain in the agri-food sector. NPC composed of synthetic polymers, proteins or polysaccharides gather interesting properties to be used for oral administration of pharmaceutics and nutraceutics. Oral administration remains the most convenient way of delivering drugs (e.g. peptides, proteins and nucleic acids) since these suffer similar metabolic pathways as food supply. Recent advances in biotechnology have produced highly potent new molecules however with low oral bioavailability. A suitable and promising approach to overcome their sensitivity to chemical and enzymatic hydrolysis as well as the poor cellular uptake, would be their entrapment within suitable gastrointestinal (GI) resistant NPC. Increasing attention has been paid to the potential use of NPC for peptides, proteins, antioxidants (carotenoids, omega fatty acids, coenzyme Q10), vitamins, probiotics, for oral administration. This review focuses on the most important materials to produce NPC for oral administration, and the most recent achievements in the production techniques and bioactives successfully delivered by these means.
- Modified rose bengal assay for surface hydrophobicity evaluation of cationic solid lipid nanoparticles (cSLN)Publication . Doktorovova, S.; Shegokar, R.; Martins-Lopes, P.; Silva, A.M.; Lopes, Carla Martins; Müller, R.H.; Souto, Eliana B.Surface hydrophobicity of nanocarriers influences protein binding and subsequently fate of nanoparticles in blood circulation. Therefore, characterization of surface hydrophobicity of nanocarriers provides important preclinical information. Here, a modified classical adsorption method for the needs of characterization of cationic solid lipid nanoparticles (cSLN) was developed. We have identified possible method limitations that should be considered when performing the analysis, i.e. the problems associated with particle separation from the dispersion and their own absorbance in visible spectrum. We propose two modified methods for performing the assay overcoming the stated limitations. We also discuss here evaluation by different approaches (calculation of binding constants or partitioning quotient) and their suitability for the prepared cSLN formulation. Overall, we confirmed that our modified adsorption method can provide useful information about surface properties of (cationic) SLN, however, performing and evaluation of the assay need special attention in order to obtain the desired results.
- Targeted Lipid Nanocarriers for TheragnosticsPublication . Souto, Eliana Maria Barbosa
- Theragnostics, Intellectual Property & EthicsPublication . Souto, Eliana Maria Barbosa
- Phospholipid-coated antipsychotic-loaded Solid Lipid Nanoparticles (SLN) for oral deliveryPublication . Silva, Ana Catarina; Santos, D.; Souto, Eliana B.; Ferreira, D.
- EditorialPublication . Sá, Maria José; Souto, Eliana B.; Martins, Luís
- Proteínas e polissacarídeos utilizados na preparação de sistemas de transporte de substâncias activasPublication . Fangueiro, Joana; Gonçalves, Ana Sofia; Souto, Eliana B.O potencial terapêutico de diferentes sistemas de transporte de substâncias activas tem sido explorado para uma grande variedade de substâncias activas, preenchendo assim vários requisitos, como a prevenção da sua eliminação rápida do organismo, a redução da toxicidade sistémica, a estabilização e a optimização do seu metabolismo, a cedência efectiva no local alvo, e permitem ainda ultrapassar o transporte limitado e os mecanismos de defesa. No entanto, têm sido reconhecidos vários outros desafios associados à cedência específica da substância activa ao local alvo, pelo que, para ultrapassar os obstáculos químicos e biológicos, a selecção do polímero utilizado para a preparação do sistema de transporte adquire especial importância. O presente artigo visa uma apresentação de alguns exemplos de polímeros naturais, nomeadamente proteínas e polissacarídeos, utilizados actualmente para a produção de micropartículas poliméricas biodegradáveis. The therapeutic potential of different drug delivery systems has been exploited for a wide variety of drugs, fulfilling several requisites, such as avoidance of a fast body clearance, reduction of systemic toxicity, stabilization and optimization of drug metabolism, effective site-specific delivery, allowing as well overcoming the limited and self-defence mechanisms. Nevertheless, several other challenges associated to site-specific drug delivery have been pointed out, thus selection of the best and most appropriate polymer to overcome the chemical and biological shortcomings is of major relevance. The present review focuses on examples of some natural polymers, namely proteins and polysaccharides, currently in use for the production of biodegradable microparticles.
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