Instituto Superior Of Ciencias Da Saude Norte

Gandra, Portugal

Instituto Superior Of Ciencias Da Saude Norte

Gandra, Portugal
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Andrade F.,University of Porto | Rafael D.,University of Lisbon | Videira M.,University of Lisbon | Ferreira D.,University of Porto | And 5 more authors.
Advanced Drug Delivery Reviews | Year: 2013

Used since ancient times especially for the local treatment of pulmonary diseases, lungs and airways are a versatile target route for the administration of both local and systemic drugs. Despite the existence of different platforms and devices for the pulmonary administration of drugs, only a few formulations are marketed, partly due to physiological and technological limitations.Respiratory infections represent a significant burden to health systems worldwide mainly due to intrahospital infections that more easily affect immune-compromised patients. Moreover, tuberculosis (TB) is an endemic infectious disease in many developing nations and it has resurged in the developed world associated with the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic.Currently, medicine faces the specter of antibiotic resistance. Besides the development of new anti-infectious drugs, the development of innovative and more efficient delivery systems for drugs that went off patent appears as a promising strategy pursued by the pharmaceutical industry to improve the therapeutic outcomes and to prolong the utilities of their intellectual property portfolio. In this context, nanotechnology-based drug delivery systems (nano-DDS) emerged as a promising approach to circumvent the limitations of conventional formulations and to treat drug resistance, opening the hypothesis for new developments in this area. © 2013 Elsevier B.V.


Das Neves J.,University of Porto | Bahia M.F.,University of Porto | Amiji M.M.,Northeastern University | Sarmento B.,University of Porto | Sarmento B.,Instituto Superior Of Ciencias Da Saude Norte
Expert Opinion on Drug Delivery | Year: 2011

Introduction: The benefits of mucoadhesive systems are related to the increased in situ residence and intimate contact of the delivery vehicle with the mucosa. The recent emergence of nanomedicine and the properties of nanoparticulate systems have created new challenges in understanding the nature and mechanisms of nanoscale mucoadhesion and in the development of methodologies for measuring its mucoadhesive potential. Even when usually regarded as an advantageous property, mucoadhesion can be an inconvenience for nanosystems, and strategies have been developed for minimizing interactions with the mucosal tissues/fluids. Areas covered: This article summarizes the basic concepts of mucoadhesion at the nanoscale, different techniques used for measuring the mucoadhesive potential of nanosystems and strategies for increasing/decreasing mucoadhesive interactions. Expert opinion: The mucoadhesion behavior of materials in bulk and at the nanoscale can significantly differ. Advances in the methodology used for studying the mucoadhesion phenomenon have contributed to its better understanding and, more importantly, the development of strategies to increase/decrease mucoadhesion. However, development of new methodologies for studying mucoadhesion at the nanoscale and the refinement of existing methodologies are still required. Also, a substantial amount of information is still lacking, particularly related to formulation issues, on how to translate lessons learnt at the bench top to the bed side. © 2011 Informa UK, Ltd.


Woitiski C.B.,University of Coimbra | Woitiski C.B.,Queen's University | Sarmento B.,University of Porto | Sarmento B.,Instituto Superior Of Ciencias Da Saude Norte | And 3 more authors.
International Journal of Pharmaceutics | Year: 2011

The effect of nanoparticulate delivery system on enhancing insulin permeation through intestinal membrane was evaluated in different intestinal epithelial models using cell cultures and excised intestinal tissues. Multilayered nanoparticles were formulated by encapsulating insulin within a core consisting of alginate and dextran sulfate nucleating around calcium and binding to poloxamer, stabilized by chitosan, and subsequently coated with albumin. Insulin permeation through Caco-2 cell monolayer was enhanced 2.1-fold, facilitated by the nanoparticles compared with insulin alone, 3.7-fold through a mucus-secreting Caco-2/HT29 co-culture, and 3.9-fold through excised intestinal mucosa of Wistar rats. Correlation of Caco-2/HT29 co-culture cells with the animal-model intestinal membrane demonstrates that the mucus layer plays a significant role in determining the effectiveness of oral nanoformulations in delivering poorly absorbed drugs. Albumin was applied to the nanoparticles as outermost coat to protect insulin through shielding from proteolytic degradation. The effect of the albumin layering on insulin permeation was compared with albumin-free nanoparticles that mimic the result of albumin being enzymatically removed during gastric and intestinal transport. Results showed that albumin layering is important toward improving insulin transport across the intestinal membrane, possibly by stabilizing insulin in the intestinal conditions. Transcellular permeation was evidenced by internalization of independently labeled insulin and nanoparticles into enterocytes, in which insulin appeared to remain associated with the nanoparticles. Transcellular transport of insulin through rat intestinal mucosa may represent the predominant mechanism by which nanoparticles facilitate insulin permeation. Nanoformulations demonstrated biocompatibility with rat intestinal mucosa through determination of cell viability via monitoring of mitochondrial dehydrogenases. Insulin permeation facilitated by the biocompatible nanoparticles suggests a potential carrier system in delivering protein-based drugs by the oral route. © 2011 Elsevier B.V. All rights reserved.


Araujo F.,Instituto Superior Of Ciencias Da Saude Norte | Araujo F.,University of Porto | Sarmento B.,Instituto Superior Of Ciencias Da Saude Norte | Sarmento B.,University of Porto
International Journal of Pharmaceutics | Year: 2013

Caco-2 based cell models have been the gold standard in vitro method to study intestinal drug permeability, despite the absence of many important features with major influence in the drug absorption mechanism. In the present work, a triple co-culture comprising Caco-2, HT29-MTX and Raji B cells was established to mimic in a closely way the human intestinal epithelium, presenting the main components in the process of drug absorption, namely the absorptive cells that resemble enterocytes, mucus producers cells and cells able to induce M-cell phenotype on Caco-2 cells. All the three cell lines maintained their function when cultured together with each other being, thus, an asset to new orally administrated drugs development. The seeding ratio of 90:10 between Caco-2 and HT29-MTX showed to be the best to achieve physiological proportions after cells maturation and differentiation in culture. The formation of M-cells phenotype from enterocytes was identified for the first time in a co-culture system comprising Caco-2 and HT29-MTX cells through immunocytochemical techniques. Thus, the triple co-culture model presented in the herein work is a good and reliable alternative to the in vitro methods already existents for the study of drugs permeability. © 2013 Elsevier B.V.


Costa A.,Instituto Superior Of Ciencias Da Saude Norte | Sarmento B.,Instituto Superior Of Ciencias Da Saude Norte | Sarmento B.,University of Porto | Seabra V.,Instituto Superior Of Ciencias Da Saude Norte
Expert Opinion on Drug Metabolism and Toxicology | Year: 2014

Introduction: Drugs are indispensable for human welfare nevertheless there is a lack of safe drugs. Obtaining pharmacokinetics information, especially metabolism, is a requirement during preclinical and clinical drug development so that in vitro tools represent a simple path where it is possible to assess drug toxicity and predict drug safety in humans. Areas covered: This review covers the latest in vitro tools developed for assessing drug toxicity in different organs. A special focus is given to hepatic models, as it is the main organ responsible for drug metabolism and consequently bioactivation and detoxification reactions. Three-dimensional culture models have been widely developed, resembling in vivo-like conditions, and are also discussed in this review. Expert opinion: Several in vitro tools to assess hepatic drug metabolism have been developed, however, novel in vitro methods to investigate extra-hepatic drug metabolism still need to be improved. These methods are able to reduce the number of animal used in preclinical experiments, but in vivo tests are mandatory for drug approval and commercialization. © 2014 Informa UK, Ltd.


Monteiro L.S.,Instituto Superior Of Ciencias Da Saude Norte | Antunes L.,Portuguese Institute of Oncology IPO Porto | Bento M.J.,Portuguese Institute of Oncology IPO Porto | Warnakulasuriya S.,King's College London
Journal of Oral Pathology and Medicine | Year: 2013

Objectives: To analyse the trends and patterns of lip, oral and oro-pharyngeal cancer incidence in Portugal between 1998 and 2007. Patients and Methods: Data on lip, oral and oro-pharyngeal cancers was collected from the databases maintained at the three main Regional Cancer Registries of Portugal (1998-2007). The data were analysed by gender, age and by site. Incidence rates were age standardized by the direct method, and joinpoint regression was used to estimate trends in incidence. Results: During this 10-year period, a total of 9623 cases of lip, oral and oropharynx cancers were reported, 7565 (78.6%) in males and 2058 (21.4%) in females. There was an increase in the age-standardized incidence of oral cancers by 1.96% per year for both sexes grouped together and an increase of 4.34% per year for the female group. Oro-pharyngeal cancer showed an increase incidence trend of 3.49% per year for both sexes grouped together and an increase of 3.49% per year for male group among the sites analysed. Lip cancer showed a decrease in its incidence rate. Conclusion: In view of rising trends, it is necessary to implement policies on oral cancer control by initiating campaigns on oral cancer awareness and screening and to harness political measures on tobacco and alcohol control for the Portuguese population. © 2012 John Wiley & Sons A/S.


das Neves J.,University of Porto | Amiji M.,Northeastern University | Sarmento B.,University of Porto | Sarmento B.,Instituto Superior Of Ciencias Da Saude Norte
Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology | Year: 2011

Topical microbicides are a promising strategy in the prevention of vaginal and rectal HIV transmission as well as other sexually transmitted pathogens. The perspective of developing nanotechnology-based systems for topical microbicides seems to be useful because important features such as enhanced drug release, targeting, and epithelial penetration can be achieved. However, the interaction of nanoparticles with the mucus fluids that cover the cervicovaginal mucosal epithelium, which can work either as a docking point or as a barrier for diffusion, has been frequently neglected. In this review, we discuss the principles of nanosystems' adhesion to the mucosal tissue and how this relates to the development of optimized microbicide formulations. © 2011 John Wiley & Sons, Inc.


Antunes F.,University of Porto | Andrade F.,University of Porto | Araujo F.,Instituto Superior Of Ciencias Da Saude Norte | Ferreira D.,University of Porto | And 2 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2013

In vitro cell culture models for studying oral drug absorption during early stages of drug development have become a useful tool in drug discovery and development, with respect to substance throughput and reproducibility. The aim of this study was to establish an in vitro cellular model based on human colon carcinoma Caco-2, mucus-producing HT29, and Raji B cells in order to design a model that more accurately mimics the small intestinal epithelial layer. Normal oriented model was set up by seeding co-cultures of Caco-2 and HT29 cells into Transwell filters and maintained under identical conditions following addition of Raji B to the basolateral chamber. Inverted model was set up seeding Caco-2 and HT29 cells on the basolateral chamber and then transferred in the Transwell device with the epithelial cells facing the basolateral chamber following Raji B addition to the apical compartment. Morphological differences on size and thickness of cell membranes were detected between the models studied by using fluorescence microscopy. On the triple co-culture models, cell membranes were increasing in size and thickness from the Caco-2 to Caco-2/HT29 and Caco-2/Raji B. Also, the nuclei seem to be larger than in the other studied models. Insulin permeation was higher on the triple co-culture model when compared to the Caco-2/HT29 co-culture model. Also, insulin permeation as mediated by nanoparticles and insulin solution permeation was higher on the normal oriented Caco-2/HT29/Raji B model as compared to the inverted model. Overall, our results suggest that Caco-2/HT29/Raji B triple co-culture normal oriented cellular model may be reliable to obtain a more physiological, functional, and reproducible in vitro model of the intestinal barrier to study protein absorption, both in solution and when delivered by nanocarriers. © 2012 Elsevier B.V. All rights reserved.


Fonte P.,Instituto Superior Of Ciencias Da Saude Norte
Biomatter | Year: 2012

PLGA nanoparticles are useful to protect and deliver proteins in a localized or targeted manner, with a long-term systemic delivery pattern intended to last for a period of time, depending on polymer bioerosion and biodegradability. However, the principal concern regarding these carriers is the hydrolytic instability of polymer in aqueous suspension. Freeze-drying is a commonly used method to stabilize nanoparticles, and cryoprotectants may be also used, to even increase its physical stability. The aim of the present work was to analyze the influence of cryoprotectants on nanoparticle stability and porosity after freeze-drying, which may influence protein release and stability. It was verified that freeze-drying significantly increased the number of pores on PLGA-NP surface, being more evident when cryoprotectants are added. The presence of pores is important in a lyophilizate to facilitate its reconstitution in water, although this may have consequences to protein release and stability. The release profile of insulin encapsulated into PLGA-NP showed an initial burst in the first 2 h and a sustained release up to 48 h. After nanoparticles freeze-drying the insulin release increased about 18% in the first 2 h due to the formation of pores, maintaining a sustained release during time. After freeze-drying with cryoprotectants, the amount of insulin released was higher for trehalose and lower for sucrose, glucose, fructose and sorbitol comparatively to freeze-dried PLGA-NP with no cryoprotectant added. Besides the porosity, the ability of cryoprotectants to be adsorbed on the nanoparticles surface may also play an important role on insulin release and stability.


Soares S.,Instituto Superior Of Ciencias Da Saude Norte | Costa A.,Instituto Superior Of Ciencias Da Saude Norte | Sarmento B.,Instituto Superior Of Ciencias Da Saude Norte | Sarmento B.,University of Porto
Expert Opinion on Drug Delivery | Year: 2012

Introduction: Insulin has usually been administered subcutaneously in the treatment of diabetes mellitus. Alternative delivery routes of insulin are expected to overcome some limitations, mainly concerned with the possibility of hypoglycemia episodes, weight gain and inadequate post-meal glucose control, in order to lead a better patient compliance. Areas covered: This review article covers all the most relevant non-invasive insulin delivery methods under development, respective technology and clinical data available according to their status of development. Special focus is given to the systems with late clinical trial evidences, their achievements and pitfalls. Pulmonary and oral appear to be the most advantageous routes, with regard to the long list of potentially marketed products. Expert opinion: Alternative insulin delivery to the subcutaneous administration is more and more close to the success, being fundamental that any optimized technology could overcome the overall low mucosal bioavailability of insulin, mostly due to its early degradation before absorption, inactivation and digestion by proteolytic enzymes and poor permeability across mucosal epithelium because of its high molecular weight and lack of lipophilicity. © 2012 Informa UK, Ltd.

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