Instituto Universitario Of Ciencias Da Saude

Gandra, Portugal

Instituto Universitario Of Ciencias Da Saude

Gandra, Portugal
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Kennedy P.J.,University of Porto | Kennedy P.J.,Abel Salazar Biomedical Sciences Institute | Oliveira C.,University of Porto | Granja P.L.,University of Porto | And 3 more authors.
Pharmacology and Therapeutics | Year: 2017

Monoclonal antibodies (mAbs) are well established in the clinic due to their specificity and affinity to a diverse array of biochemical targets. More recently, mAbs are being exploited as targeting agents in modern drug delivery systems, aiming to bypass normal host tissue and to accumulate a therapeutic agent to a specific tissue or cell for enhanced pharmacology. At sizes ranging from ~. 10-100. nm, antibody-based bioconjugates have opened up a whole new realm of clinical possibilities with several platforms emerging on the market. Antibody-drug conjugates combine the killing power of cytotoxic agents with mAb specificity and have great potential to treat cancer and beyond. Partnering a mAb with a biologic (protein/peptide, oligonucleotide (ON) or another mAb) is also gaining clinical traction. For example, many bispecific mAbs target and recruit immune effector cells to a tumor, while ON-based therapeutics against intracellular (regulatory) RNAs may be safely delivered into specific cells with mAb support. Finally, nanoparticles (NPs) offer significant drug delivery advantages including controlled release, large and diverse payloads, intracellular delivery and multi-functionality. Coupling mAbs to the surface of NPs can add further targeting capacity, and yet, therapeutic mAbs can also be encapsulated to take advantage of the above NP qualities. Here, we present an updated overview of the different aspects required for the successful development and engineering of antibody bioconjugates in current and emerging drug delivery technologies. © 2017 Elsevier Inc.

Vasconcelos T.,BIAL Portela and Ca S.A. | Vasconcelos T.,Abel Salazar Biomedical Sciences Institute | Vasconcelos T.,University of Porto | Marques S.,University of Porto | And 3 more authors.
Advanced Drug Delivery Reviews | Year: 2016

Amorphous products and particularly amorphous solid dispersions are currently one of the most exciting areas in the pharmaceutical field. This approach presents huge potential and advantageous features concerning the overall improvement of drug bioavailability.Currently, different manufacturing processes are being developed to produce amorphous solid dispersions with suitable robustness and reproducibility, ranging from solvent evaporation to melting processes. In the present paper, laboratorial and industrial scale processes were reviewed, and guidelines for a rationale selection of manufacturing processes were proposed. This would ensure an adequate development (laboratorial scale) and production according to the good manufacturing practices (GMP) (industrial scale) of amorphous solid dispersions, with further implications on the process validations and drug development pipeline. © 2016 Elsevier B.V.

Fonte P.,University of Porto | Fonte P.,Instituto Universitario Of Ciencias Da Saude | Araujo F.,University of Porto | Seabra V.,Instituto Universitario Of Ciencias Da Saude | And 4 more authors.
International Journal of Pharmaceutics | Year: 2015

The purpose of this work was to evaluate the influence of the co-encapsulation of lyoprotectants with insulin into PLGA nanoparticles, on the stability of the protein and nanoparticles upon lyophilization. Different lyoprotectants were used, namely trehalose, glucose, sucrose, fructose and sorbitol at 10% (w/v). Insulin-loaded PLGA nanoparticles with co-encapsulated lyoprotectants achieved a mean particle size of 386-466 nm, and a zeta potential ranging between -34 and -38 mV, dependent on the lyoprotectant used. Formulations had association efficiencies and loading capacities of 85-91% and 10-12%, respectively. The lyophilization process increased the colloidal stability of nanoparticles, and maintained their spherical shape and smooth surface, particularly in presence of lyoprotectants. XRPD revealed that the lyophilizates of nanoparticles with co-encapsulated lyoprotectants were amorphous, whereas formulations with externally added lyoprotectants, except trehalose, showed crystallinity. FTIR assessment showed that co-encapsulating lyoprotectants better preserved insulin structure upon lyophilization with a spectral area overlap of 82-87%, compared to only 72% in lyoprotectant absence. These results were confirmed by circular dichroism spectroscopy. Surprisingly, the simultaneous co-encapsulation and addition of lyoprotectants was detrimental to protein stabilization. The insulin in vitro release studies demonstrated that formulations with co-encapsulated trehalose, glucose, sucrose, fructose and sorbitol achieved 83%, 69%, 70%, 77% and 74%, respectively after 48 h. In contrast, formulations added with those lyoprotectants prior lyophilization showed a lower release rate not higher than 60% after 48 h. This work gives rise to a different promising strategy of co-encapsulating lyoprotectants and therapeutic proteins, to better stabilize protein structure upon lyophilization. © 2015 Elsevier B.V. All rights reserved.

PubMed | Abel Salazar Biomedical Sciences Institute, Hospital Clinico Universitario Virgen la Arrixaca, Pennine Acute Hospitals NHS Trust, Instituto Universitario Of Ciencias Da Saude and University of Birmingham
Type: | Journal: International dental journal | Year: 2016

To determine the frequency and spectrum of oral and maxillofacial lesions biopsied in a hospital population in the northern region of Portugal.We conducted descriptive analyses of pathology reports from biopsies of oral and maxillofacial lesions performed between 1990 and 2006, in Oporto Hospital Center. Information on gender and age of patient, location of the lesions and the histopathological diagnosis were analysed.The analyses revealed that 1,520 (47.7%) patients were male and 1,666 (52.3%) were female. They had a mean age standard deviation of 47.8 18.6 years. The site most frequently biopsied was the labial mucosa (17.5%). A non-neoplastic diagnosis was established in 2,162 (63.3%) cases, potentially malignant disorders in 163 (5.1%) and neoplasms in 886 (27.6%) (403 benign and 483 malignant). The most commonly reported diagnosis was fibroepithelial polyp (n = 186; 15.9%), followed by squamous cell carcinoma (SCC) (n = 158; 13.6%). SCC was the lesion most commonly found in male patients (n = 279; 18.4%) whilst fibroepithelial polyp was the lesion most commonly found in female patients (n = 268; 16.1%). The most common lesion in patients 0-17 years of age was a follicular cyst (n = 25; 12.8%), whereas in patients 18-64 years of age it was a fibroepithelial polyp (n = 299; 13%). SCC was the most common type of lesion found in patients 65 years of age (n = 160; 24.6%).This large sample provides useful information about the incidence and distribution of oral biopsies over a period of 16 years, allowing valuable comparison with other countries. Non-neoplastic lesions were the types of lesion most commonly reported, with fibroepithelial polyp being most frequent. SCC was the second most common diagnosis.

PubMed | University of Porto, Instituto Universitario Of Ciencias Da Saude and University of Sao Paulo
Type: | Journal: Drug delivery and translational research | Year: 2017

In this work, self-assembled amphiphilic micelles based on chitosan (CS) and polycaprolactone (PCL) were produced and used as carriers of paclitaxel (PTX) to improve its intestinal pharmacokinetic profile. Chitosan-grafted-polycaprolactone (CS-g-PCL) was synthesized through a carbodiimide reaction by amidation and confirmed by Fourier transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance analysis (

PubMed | University of Porto, Northeastern University and Instituto Universitario Of Ciencias Da Saude
Type: Journal Article | Journal: Molecular pharmaceutics | Year: 2015

Development of efficient and versatile drug delivery platforms to overcome the physical and biological challenges in cancer therapeutics is an area of great interest, and novel materials are actively sought for such applications. Recent strides in polymer science have led to a combinatorial approach for generating a library of materials with different functional identities that can be mixed and matched to attain desired characteristics of a delivery vector. We have applied the combinatorial design to chitosan (CS), where the polymer backbone has been modified with polyethylene glycol, epidermal growth factor receptor-binding peptide, and lipid derivatives of varying chain length to encapsulate hydrophobic drugs. Cisplatin, cis-([PtCl2(NH3)2]), is one of the most potent chemotherapy drugs broadly administered for cancer treatment. Cisplatin is a hydrophilic drug, and in order for it to be encapsulated in the developed nanosystems, it was modified with lipids of varying chain length. The library of four CS derivatives and six platinum derivatives was self-assembled in aqueous medium and evaluated for physicochemical characteristics and cytotoxic effects in platinum-sensitive and -resistant lung cancer cells. The results show that the lipid-modified platinate encapsulation into CS nanoparticles significantly improved cellular cytotoxicity of the drug. In this work, we have also reinforced the idea that CS is a multifaceted system that can be as successful in delivering small molecules as it has been as a nucleic acids carrier.

Martins J.P.,University of Porto | Kennedy P.J.,University of Porto | Santos H.A.,Aalto University | Barrias C.,University of Porto | And 2 more authors.
Pharmacology and Therapeutics | Year: 2016

Advances in the understanding of neonatal Fc receptor (FcRn) biology and function have demonstrated that this receptor, primarily identified for the transfer of passive immunity from mother infant, is involved in several biological and immunological processes. In fact, FcRn is responsible for the long half-life of IgG and albumin in the serum, by creating an intracellular protein reservoir, which is protected from lysosomal degradation and, importantly, trafficked across the cell. Such discovery has led researchers to hypothesize the role for this unique receptor in the controlled delivery of therapeutic agents. A great amount of FcRn-based strategies are already under extensive investigation, in which FcRn reveals to have profound impact on the biodistribution and half-life extension of therapeutic agents. This review summarizes the main findings on FcRn biology, function and distribution throughout different tissues, together with the main advances on the FcRn-based therapeutic opportunities and model systems, which indicate that this receptor is a potential target for therapeutic regimen modification. © 2016 Elsevier Inc. All rights reserved.

PubMed | University of Porto and Instituto Universitario Of Ciencias Da Saude
Type: Journal Article | Journal: International orthodontics | Year: 2016

The objective of this study was to compare the dimensional changes in the alveolar ridge before, at the end of, and one year after orthodontic treatment in cases of Maxillary Lateral Incisor Agenesis and the possibility of using plaster models and panoramic radiographs as substitutes for cone beam-computed tomography.A total of 228 measurements were performed on plaster models and panoramic radiographs: before (T1), at the end of (T2), and 1 year after orthodontic treatment (T3). At stage T2, the cone beam-computed tomography was also analyzed. Non-parametric tests were used.In all 3 stages, there was no statistically significant difference regarding the thickness of the models, the height of the bone in the panoramic radiographs, the space opening and the height of the bone in the panoramic radiographs, or the space opening in the models and the thickness in the same plaster models. However, a statistically significant difference was observed for the width in the panoramic radiograph during all 3 stages. Cone beam-computed tomography did not reveal a statistically significant correlation regarding the height and width of the bone compared with the panoramic radiographs, and the thickness as compared with plaster models.There was no significant variation in thickness, height and width of the bone over time. It was demonstrated that plaster models and panoramic radiographs do not appear to be good substitutes for cone beam-computed tomography for these specific measurements.

PubMed | Instituto Universitario Of Ciencias Da Saude
Type: Journal Article | Journal: International orthodontics | Year: 2016

The objective of this study was to evaluate perception of the smile in maxillary lateral incisor agenesis (MLIA) cases treated by mesialization of a canine.Nine images were digitally modified from the same frontal intraoral photograph to simulate various treatment options for space closure in MLIA. A questionnaire was submitted to laypersons (303), general dentists (215), prosthodontists (55) and orthodontists (81). Statistical tests with a significance level of P<0.05 were used.The views of MLIA treatment judged to be most attractive showed unilateral dental and gingival reshaping. All study groups considered the simple dental reshaping of the mesial edge of the canine to be attractive. In the analysis of the images grouped together for both unilateral and bilateral MLIA, the view showing dental and gingival reshaping was considered the most attractive whereas unmodified mesialization was considered the least attractive.Regarding the space closure treatments, although all groups regarded simple dental reshaping of the canine to be attractive, the dental professionals considered gingival and crown reshaping to be more esthetic. In contrast, laypersons were not significantly responsive to this dental and gingival modification as compared to only slight reshaping of the mesial edge of the cusp of the mesialized canine in MLIA.

PubMed | Instituto Universitario Of Ciencias Da Saude
Type: | Journal: Death studies | Year: 2016

In 2001, in Entre-os-Rios, Portugal, a bridge fell on Douro River, all 59 passengers from one bus and three cars died and 36 bodies have never been recovered. The objective is to reveal the cumulative risk from multiple losses and unrecovered bodies, 10 years after, comparing with grievers from road accidents. There are two groups of relatives of victims: from this tragedy (n = 20), with at least one unrecovered body; and from road traffic accidents (n = 20), with the same time after loss. The prevalence of prolonged grief was 95% and for traumatic stress was 70%. The associated factors of multiple losses and unrecovered bodies increase the long-term risk (RR = 1.6 to 2.8; R

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