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- Ciclodextrinas: formação de complexos e sua aplicação farmacêuticaPublication . Oliveira, Rita; Santos, Delfim; Barata, PedroO número de moléculas com problemas de solubilidade, biodisponibilidade e permeabilidade tem vindo a aumentar. As ciclodextrinas são oligossacarídeos cíclicos com uma cavidade central hidrófoba, cuja estrutura permite formar complexos de inclusão estáveis com diversos fármacos. A complexação com ciclodextrinas permite optimizar os diversos sistemas transportadores constituídos por este tipo de fármacos, assim como solucionar problemas devidos a propriedades indesejáveis como instabilidade, más características organolépticas ou potencial irritação. The number of molecules with problems of solubility, bioavailability and permeability is increasing. Cyclodextrins are cyclic oligosaccharides with a hydrophobic central cavity, whose structure can form stable inclusion complexes with various drugs. Complexation allows the optimization of drug delivery of such drugs, and to solve problems due to undesirable properties such as instability, poor organoleptic characteristics or irritation.
- Tecnologia Farmacêutica II - trabalhos laboratoriais em vídeoPublication . Oliveira, Rita
- Manual de apoio pedagógico: Tecnologia Farmacêutica IIPublication . Oliveira, Rita
- Effect of cyclodextrins and pH on the permeation of tetracaine: supramolecular assemblies and release behaviorPublication . Teixeira, Raquel S.; Veiga, Francisco J.B.; Oliveira, Rita; Jones, Stuart A.; Silva, Sérgio M.C.; Carvalho, Rui A.; Valente, Artur J.M.This work provides a new insight on fundamental principles of the interaction mechanism between two forms of tetracaine – a potent local anesthetic – both in neutral (TC) and ionized (TC+) states, with beta- (b-CD) and hydroxypropyl-beta-cyclodextrin (HP-b-CD), and how such interactions affect the transport of tetracaine, at different concentrations, across a model membrane. The kinetics and mechanism of TC release from HPMC gels is also evaluated giving an insight on the role of cyclodextrin on the tetracaine transport. HPLC, fluorescence and NMR spectroscopies provided solid physicochemical knowledge of these systems and in vitro studies were performed to obtain relevant data on the transport and mechanism parameters. HPLC and fluorescence spectroscopy data revealed that tetracaine interacts with both cyclodextrins on a 1:1 stoichiometry but it is observed that neutral tetracaine forms more stables complexes (ca. 1050 M 1 for both cyclodextrins) than in its ionized form (628 and 337 M 1 for b-CD and HP-b-CD respectively). Despite of that, no host–guest interactions take place as seen by ROESY. This study clearly demonstrates that both forms of tetracaine are successfully released from the formulations at a controlled rate, following a Super-Case transport mechanism and the transport of tetracaine can be tuned by using cyclodextrins.
- Influence of gut microbiota dysbiosis on brain function: a systematic reviewPublication . Almeida, Cátia; Oliveira, Rita; Soares, Raquel; Barata, PedroBackground: For almost a century it has been recognized that human possess a varied and dens microbial ecosystem called the human microbiota, yet we are still beginning to understand many of the roles that these microorganisms play in human health and development. It is thought that under certain circumstances such as dysbiosis, the microbiota can cause diseases, where the central nervous system (CNS) has an important relevance and where the “gut-brain axis” will play a major role. Aims: This review investigated the influence of the gut microbiota on brain function, trying to demonstrate whether dysbiosis influences CNS diseases or whether it is the disease that causes dysbiosis, highlighting the existing literature within this field. Methods:We performed a systematic literature search in EMBASE, PubMed, and Cochrane combining the terms “gut microbiota,” “dysbiosis,” and “CNS diseases” to identify those whom reported some influence or relation between dysbiosis of gut microbiota and CNS diseases. For the present systematic review, we only included systematic reviews or meta-analysis. Results: The EMBASE, PubMed, and Cochrane were systematically searched, considering only systematic reviews or metaanalysis. Nine studies comprising 705 articles were included in this review. Those 9 systematic reviews consist in 2 about autism spectrum disorder, 1 in dementia, 1 in depression, 2 in autoimmune diseases, 1 in schizophrenia, and 2 in some altered brain function. Available data characterizing several neural diseases demonstrate a significant correlation between dysbiosis and CNS diseases, strengthen the evidence that dysbiosis of gut microbiota may correlate with abnormalities in CNS patients. Conclusions: Although there is a clear need for more investigations to better understand the role of the gut microbiota in CNS diseases, the modulation of the nervous system by the microbiota is clear, continuing to be the subject of continuous research. We need to fully understand the mechanisms by which the microbiota interacts with the human brain, and therefore what’s the connection between dysbiosis and pathologies such depression, dementia, autism, or schizophrenia.
- Protocolos laboratoriais de Tecnologia Farmacêutica IIPublication . Oliveira, Rita
- Preparation of supramolecular hydrogels containing poloxamers and methyl-β-cyclodextrinPublication . Garcia, Maria; Ruivo, Joana; Oliveira, Rita; Figueiras, AnaMeloxicam is a non-steroidal anti-inflammatory drug used in the treatment of rheumatoid arthritis, osteoarthritis and other inflammatory diseases. However, its prolonged use is associated to several side effects like gastrointestinal perforations, ulcerations and bleeding, probably due its low aqueous solubility and wettability after oral administration. These side effects can reduce patient compliance and discourage physician from prescribing this drug. In this way, inclusion complexes between meloxicam and methyl-β-cyclodextrin were prepared in aqueous solution by phase solubility studies and in solid state by freeze-drying method in order to increase drug solubility. The physicochemical characterization of the prepared complexes in solid state was performed by different techniques. Furthermore, hydrogels containing poloxamers were prepared for topical administration of meloxicam. For this purpose, solid inclusion complexes were incorporated in hydrogels with different poloxamers composition. The rheological behaviour of these formulations was studied by different methods and the drug release from optimised hydrogels was evaluated by Franz diffusion cells, applying some mathematical models to analyse the drug release mechanism from hydrogels. Results from phase solubility studies showed the formation of inclusion complexes between meloxicam and methyl-beta-cyclodextrin in aqueous solution in a 1:1 stoichiometry and an increase in drug solubility. Different techniques employed indicated complete formation of complexes in solid state prepared by the freeze-drying method. Moreover, the performed set of rheological studies, easily adapted to similar systems, demonstrated that hydrogels containing poloxamers and cyclodextrin may provide a suitable supramolecular platform for meloxicam delivery as a novel strategy to increase drug bioavailability.
- Chapter 5: Stimuli-responsive nanosystems for drug-targeted deliveryPublication . Lopes, Carla Martins; Barata, Pedro; Oliveira, Rita
- Topical probiotics: the future of dermatology to improve the health of the skin microbiomePublication . Schutz, Francine; Barata, Pedro; Oliveira, Rita
- Novel serine-based gemini surfactants as chemical permeation enhancers of local anesthetics: a comprehensive study on structure–activity relationships, molecular dynamics and dermal deliveryPublication . Teixeira, Raquel S.; Cova, Tânia F.G.G.; Silva, Sérgio M.C.; Oliveira, Rita; do Vale, M. Luísa C.; Marques, Eduardo F.; Pais, Alberto A.C.C.; Veiga, Francisco J.B.This work aims at studying the efficacy of a series of novel biocompatible, serine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine, combining an experimental and computational approach. The surfactants consist of gemini molecules structurally related, but with variations in headgroup charge (nonionic vs. cationic) and in the hydrocarbon chain lengths (main and spacer chains). In vitro permeation and molecular dynamics studies combined with cytotoxicity profiles were performed to investigate the permeation of both drugs, probe skin integrity, and rationalize the interactions at molecular level. Results show that these enhancers do not have significant deleterious effects on the skin structure and do not cause relevant changes on cell viability. Permeation across the skin is clearly improved using some of the selected serine-based gemini surfactants, namely the cationic ones with long alkyl chains and shorter spacer. This is noteworthy in the case of ropivacaine hydrochloride, which is not easily administered through the stratum corneum. Molecular dynamics results provide a mechanistic view of the surfactant action on lipid membranes that essentially corroborate the experimental observations. Overall, this study suggests the viability of these serine-based surfactants as suitable and promising delivery agents in pharmaceutical formulations.