INEB Institute Engineering Biomedica


INEB Institute Engineering Biomedica

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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.

Sarmento B.,Instituto Superior Of Ciencias Da Saude Norte | Sarmento B.,INEB Institute Engineering Biomedica | Andrade F.,University of Porto | Da Silva S.B.,University of Porto | And 4 more authors.
Expert Opinion on Drug Metabolism and Toxicology | Year: 2012

In vitro cell models have been used to predict drug permeation in early stages of drug development, since they represent an easy and reproducible method, allowing the tracking of drug absorption rate and mechanism, with an advantageous costbenefit ratio. Such cell-based models are mainly composed of immortalized cells with an intrinsic ability to grow in a monolayer when seeded in permeable supports, maintaining their physiologic characteristics regarding epithelium cell physiology and functionality. Areas covered: This review summarizes the most important intestinal, pulmonary, nasal, vaginal, rectal, ocular and skin cell-based in vitro models for predicting the permeability of drugs. Moreover, the similitude between in vitro cell models and in vivo conditions are discussed, providing evidence that each model may provisionally resemble different drug absorption route. Expert opinion: Despite the widespread use of in vitro cell models for drug permeability and absorption evaluation purposes, a detailed study on the properties of these models and their in vitroin vivo correlation compared with human data are required to further use in order to consider a future drug discovery optimization and clinical development. © 2012 Informa UK, Ltd.

Soddu E.,University of Sassari | Rassu G.,University of Sassari | Giunchedi P.,University of Sassari | Sarmento B.,CESPU Institute Investigacao e Formacao Avancada em Ciencias e Tecnologias da Saude | And 2 more authors.
European Journal of Pharmaceutical Sciences | Year: 2015

Central nervous system (CNS) diseases are hard to diagnose and therapeutically target due to the blood brain barrier (BBB), which prevents most drugs from reaching their sites of action within the CNS. Brain drug delivery systems were conceived to bypass the BBB and were derived from anatomical and functional analysis of the BBB; this analysis led researchers to take advantage of brain endothelial membrane physiology to allow drug access across the BBB. Both receptors and carriers can be used to transport endogenous and exogenous substances into the CNS. Combining a drug with substances that take advantage of these internalization mechanisms is a widely exploited strategy for drug delivery because it is an indirect method that overcomes the BBB in a non-invasive way and is therefore less dangerous and costly than invasive methods. Neurotoxins, among other naturally-occurring substances, may be used as drug carriers to specifically target the CNS. This review covers the current delivery systems that take advantage of the non-toxic components of neurotoxins to overcome the BBB and reach the CNS. We hope to give insights to researchers toward developing new delivery systems that exploit the positive features of substances usually regarded as natural hazards. © 2015 Elsevier B.V. All rights reserved.

Santos J.L.,University of Madeira | Oliveira H.,INEB Institute Engineering Biomedica | Oliveira H.,University of Porto | Pandita D.,University of Madeira | And 6 more authors.
Journal of Controlled Release | Year: 2010

A new family of gene delivery vectors is synthesized consisting of a medium-size generation PAMAM dendrimer (generation 5, with amine termini) core randomly linked at the periphery to hydrophobic chains that vary in length (12 to 16 carbon alkyl chains) and number (from 4.2 to 9.7 in average). The idea subjacent to the present work is to join the advantages of the cationic nature of the dendrimer with the capacity of lipids to interact with biological membranes. Unlike other amphiphilic systems designed for the same purpose, where the hydrophobic and hydrophilic moieties coexist in opposite sides, the present vectors have a hydrophilic interior and a hydrophobic corona. The vectors are characterized in respect to their ability to neutralize, bind and compact plasmid DNA (pDNA). The complexes formed between the vectors and pDNA are analyzed concerning their size, ζ-potential, resistance to serum nucleases, capacity of being internalized by cells and transfection efficiency. These new vectors show a remarkable capacity for mediating the internalization of pDNA with minimum cytotoxicity, being this effect positively correlated with the -CH2- content present in the hydrophobic corona. Gene expression in MSCs, a cell type with relevancy in the regenerative medicine clinical context, is also enhanced using the new vectors but, in this case, the higher efficiency is shown by the vectors containing the smallest hydrophobic chains. © 2010 Elsevier B.V.

Maia F.R.,INEB Institute Engineering Biomedica | Maia F.R.,University of Porto | Bidarra S.J.,INEB Institute Engineering Biomedica | Granja P.L.,INEB Institute Engineering Biomedica | And 3 more authors.
Acta Biomaterialia | Year: 2013

Human mesenchymal stem cells (MSCs) are currently recognized as a powerful cell source for regenerative medicine, notably for their capacity to differentiate into multiple cell types. The combination of MSCs with biomaterials functionalized with instructive cues can be used as a strategy to direct specific lineage commitment, and can thus improve the therapeutic efficacy of these cells. In terms of biomaterial design, one common approach is the functionalization of materials with ligands capable of directly binding to cell receptors and trigger specific differentiation signaling pathways. Other strategies focus on the use of moieties that have an indirect effect, acting, for example, as sequesters of bioactive ligands present in the extracellular milieu that, in turn, will interact with cells. Compared with complex biomolecules, the use of simple compounds, such as chemical moieties and peptides, and other small molecules can be advantageous by leading to less expensive and easily tunable biomaterial formulations. This review describes different strategies that have been used to promote substrate-mediated guidance of osteogenic differentiation of immature osteoblasts, osteoprogenitors and MSCs, through chemically conjugated small moieties, both in two- and three-dimensional set-ups. In each case, the selected moiety, the coupling strategy and the main findings of the study were highlighted. The latest advances and future perspectives in the field are also discussed. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Gomes M.J.,INEB Institute Engineering Biomedica | Martins S.,University of Southern Denmark | Sarmento B.,INEB Institute Engineering Biomedica | Sarmento B.,Institute Investigacao e Formacao Avancada em Ciencias e Tecnologias da Saude
Ageing Research Reviews | Year: 2015

As the population ages, brain pathologies such as neurodegenerative diseases and brain cancer increase their incidence, being the need to find successful treatments of upmost importance. Drug delivery to the central nervous system (CNS) is required in order to reach diseases causes and treat them. However, biological barriers, mainly blood-brain barrier (BBB), are the key obstacles that prevent the effectiveness of possible treatments due to their ability to strongly limit the perfusion of compounds into the brain. Over the past decades, new approaches towards overcoming BBB and its efflux transporters had been proposed. One of these approaches here reviewed is through small interfering RNA (siRNA), which is capable to specifically target one gene and silence it in a post-transcriptional way. There are different possible functional proteins at the BBB, as the ones responsible for transport or just for its tightness, which could be a siRNA target. As important as the effective silence is the way to delivery siRNA to its anatomical site of action. This is where nanotechnology-based systems may help, by protecting siRNA circulation and providing cell/tissue-targeting and intracellular siRNA delivery. After an initial overview on incidence of brain diseases and basic features of the CNS, BBB and its efflux pumps, this review focuses on recent strategies to reach brain based on siRNA, and how to specifically target these approaches in order to treat brain diseases. © 2015 Elsevier B.V.

Bidarra S.J.,INEB Institute Engineering Biomedica | Bidarra S.J.,University of Porto | Barrias C.C.,INEB Institute Engineering Biomedica | Fonseca K.B.,INEB Institute Engineering Biomedica | And 6 more authors.
Biomaterials | Year: 2011

Cell-based therapies offer an attractive approach for revascularization and regeneration of tissues. However, and despite the pressing clinical needs for effective revascularization strategies, the successful immobilization of viable vascular cells within 3D matrices has been difficult to achieve. In this paper the in vitro potential of a natural, injectable RGD-alginate hydrogel as an in situ forming matrix to deliver endothelial cells was evaluated. Several techniques were employed to investigate how these microenvironments could influence the behavior of vascular cells, namely their ability to promote the outward migration of viable, proliferative cells, retaining the ability to form a 3D arrangement. Cells within RGD-grafted alginate hydrogel were able to proliferate and maintained 80% of viability for at least 48 h post-immobilization. Additionally, entrapped cells created a 3D organization into cellular networks and, when put in contact with matrigel, cells migrated out of the RGD-matrix. Overall, the obtained results support the idea that the RGD peptides conjugated to alginate provide a 3D environment for endothelial cells adhesion, survival, migration and organization. © 2011 Elsevier Ltd.

Bidarra S.J.,INEB Institute Engineering Biomedica | Bidarra S.J.,University of Porto | Barrias C.C.,INEB Institute Engineering Biomedica | Barbosa M.A.,INEB Institute Engineering Biomedica | And 4 more authors.
Biomacromolecules | Year: 2010

In this work, human mesenchymal stem cells (hMSC) immobilized in RGD-coupled alginate microspheres, with a binary composition of high and low molecular weight alginate, were investigated. Cells immobilized within RGD-alginate microspheres (during 21 days) showed metabolic activity, with an overall viability higher than 90%, short cell extensions, and, when induced, they were able to differentiate into the osteogenic lineage. In osteogenic conditions (comparing to basal conditions), immobilized cells presented alkaline phosphatase (ALP) activity and an upregulation of ALP, collagen type I, and Runx 2 expression. Moreover, mineralization was also detected in immobilized cells under osteogenic stimulus. In addition, it was demonstrated for the first time that MSCs immobilized in this 3D matrix were able to enhance the ability of neighboring endothelial cells to form tubelike structures. Overall, these findings represent a step forward in the development of injectable stem cell carriers for bone tissue engineering. © 2010 American Chemical Society.

Debasu M.L.,University of Aveiro | Ananias D.,University of Aveiro | Pinho S.L.C.,INEB Institute Engineering Biomedica | Geraldes C.F.G.C.,University of Coimbra | And 2 more authors.
Nanoscale | Year: 2012

Up-conversion (Gd,Yb,Tb)PO 4 materials and their potential for bimodal imaging have received little attention in the literature. Herein, we report the first study on the up-conversion emission of (Gd,Yb,Tb)PO 4 nanocrystals synthesized via a hydrothermal method at 150°C. These materials exhibit ultraviolet, blue and green up-conversion emissions upon excitation with a 980 nm continuous wave laser diode. The intensity of the blue-emission band at 479 nm, ascribed to the cooperative up-conversion emission of a pair of excited Yb 3+ ions, depends on the Yb 3+/Tb 3+ concentration ratio, calcination temperature and particle size. Strong green up-conversion emission of Tb 3+ is observed at 543 nm for the 5D 4 → 7F 5 transition. Relaxometry measurements reveal that the nanocrystals are efficient T 2-weighted (negative) contrast agents which, combined with visible-light emission generated by infrared excitation, affords them considerable potential for being used in bimodal, photoluminescence-magnetic resonance, imaging. © 2012 The Royal Society of Chemistry.

Almeida C.R.,INEB Institute Engineering Biomedica | Vasconcelos D.P.,INEB Institute Engineering Biomedica | Vasconcelos D.P.,Abel Salazar Biomedical Sciences Institute | Goncalves R.M.,INEB Institute Engineering Biomedica | And 2 more authors.
Journal of the Royal Society Interface | Year: 2012

An exacerbated inflammatory response questions biomaterial biocompatibility, but on the other hand, inflammation has a central role in the regulation of tissue regeneration. Therefore, it may be argued that an 'ideal' inflammatory response is crucial to achieve efficient tissue repair/regeneration. Natural killer (NK) cells, being one of the first populations arriving at an injury site, can have an important role in regulating bone repair/regeneration, particularly through interactions with mesenchymal stem/stromal cells (MSCs). Here, we studied how biomaterials designed to incorporate inflammatory signals affected NK cell behaviour and NK cell-MSC interactions. Adsorption of the pro-inflammatory molecule fibrinogen (Fg) to chitosan films led to a 1.5-fold increase in adhesion of peripheral blood human NK cells, without an increase in cytokine secretion. Most importantly, it was found that NK cells are capable of stimulating a threefold increase in human bone marrow MSC invasion, a key event taking place in tissue repair, but did not affect the expression of the differentiation marker alkaline phosphatase (ALP). Of significant importance, this NK cell-mediated MSC recruitment was modulated by Fg adsorption. Designing novel biomaterials leading to rational modulation of the inflammatory response is proposed as an alternative to current bone regeneration strategies. © 2011 The Royal Society.

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