Browsing by Author "Reis, Salette"
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- Docosahexaenoic acid loaded lipid nanoparticles with bactericidal activity against Helicobacter pylonPublication . Seabra, Catarina Leal; Nunes, Claudia; Gomez-Lazaro, Maria; Correia, Maria Marta; Machado, José Carlos; Gonçalves, Inês C.; Reis, Celso A.; Reis, Salette; Martins, M. Cristina L.Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid present in fish oil, has been described as a promising molecule to the treatment of Helicobacter pylori gastric infection. However, due to its highly unsaturated structure, DHA can be easily oxidized loosing part of its bioactivity. This work aims the nanoencapsulation of DHA to improve its bactericidal efficacy against H. pylori. DHA was loaded into nanostructured lipid carriers (NLC) produced by hot homogenization and ultrasonication using a blend of lipids (Precirol AT05 (R), Miglyol-812 (R)) and a surfactant (Tween 60 (R)). Homogeneous NLC with 302 +/- 14 nm diameter,-28 +/- 3 mV surface charge (dynamic and electrophoretic light scattering) and containing 66 +/- 7% DHA (UV/VIS spectroscopy) were successfully produced. Bacterial growth curves, performed over 24 h in the presence of different DHA concentrations (free or loaded into NLC), demonstrated that nanoencapsulation enhanced DHA bactericidal effect, since DHA-loaded NLC were able to inhibit H. pylori growth in a much lower concentrations (25 mu M) than free DHA (>100 mu M). Bioimaging studies, using scanning and transmission electron microscopy and also imaging flow cytometry, demonstrated that DHA-loaded NLC interact with H. pylori membrane, increasing their periplasmic space and disrupting membrane and allowing the leakage of cytoplasmic content. Furthermore, the developed nanoparticles are not cytotoxic to human gastric adenocarcinoma cells at bactericidal concentrations. DHA-loaded NLC should, therefore, be envisaged as an alternative to the current treatments for H. pylori infection. (C) 2017 Elsevier B.V. All rights reserved.
- Evaluation of the antitumour and antiproliferative effect of Xanthohumol-Loaded PLGA nanoparticles on melanomaPublication . Fonseca, Magda; Macedo, Ana S.; Lima, Sofia A. Costa; Reis, Salette; Soares, Raquel; Fonte, PedroCutaneous melanoma is the deadliest type of skin cancer and current treatment is still inadequate, with low patient survival rates. The polyphenol xanthohumol has been shown to inhibit tumourigenesis and metastasization, however its physicochemical properties restrict its application. In this work, we developed PLGA nanoparticles encapsulating xanthohumol and tested its antiproliferative, antitumour, and migration effect on B16F10, malignant cutaneous melanoma, and RAW 264.7, macrophagic, mouse cell lines. PLGA nanoparticles had a size of 312 ± 41 nm and a PdI of 0.259, while achieving a xanthohumol loading of about 90%. The viability study showed similar cytoxicity between the xanthohumol and xanthohumol-loaded PLGA nanoparticles at 48 h with the IC50 established at 10 µM. Similar antimigration effects were observed for free and the encapsulated xanthohumol. It was also observed that the M1 antitumor phenotype was stimulated on macrophages. The ultimate anti-melanoma effect emerges from an association between the viability, migration and macrophagic phenotype modulation. These results display the remarkable antitumour effect of the xanthohumol-loaded PLGA nanoparticles and are the first advance towards the application of a nanoformulation to deliver xanthohumol to reduce adverse effects by currently employed chemotherapeutics.
- Nanocarrier-mediated topical insulin delivery for wound healingPublication . Macedo, Ana S.; Mendes, Francisca; Filipe, Patrícia; Reis, Salette; Fonte, PedroWound care has been clinically demanding due to inefficacious treatment that represents an economic burden for healthcare systems. In Europe, approximately 7 million people are diagnosed with untreated wounds, leading to a cost between 6.000€ and 10.000€ per patient/year. In the United States of America, 1.5 million people over 65 years old suffer from chronic wounds. A promising therapeutic strategy is the use of exogenous growth factors because they are decreased at the wound site, limiting the recovery of the skin. Insulin is one of the cheapest growth factors in the market able to accelerate the re-epithelialization and stimulate angiogenesis and cell migration. However, the effectiveness of topical insulin in wound healing is hampered by the proteases in the wound bed. The encapsulation into nanoparticles improves its stability in the wound, providing adhesion to the mucosal surface and allowing its sustained release. The aim of this review is to perform a standing point about a promising strategy to treat different types of wounds by the topical delivery of insulin-loaded nanocarriers.
- Nanomedicine interventions in clinical trials for the treatment of metastatic breast cancerPublication . Moreira, Rita; Granja, Andreia; Pinheiro, Marina; Reis, SaletteBreast cancer was responsible for the deaths of 626,679 women in 2018. After decades of research, the mortality rates remain high. While the barrier of selectively killing tumor cells is not yet overcome, the search for targeted therapeutics continues. The use of nanomedicine in cancer treatment has opened up new possibilities for more precise drug-delivery systems. This review aimed to gather information and analyze recent clinical trials evaluating the therapeutic effects of nanoparticles in the treatment of metastatic breast cancer. To accomplish this, the clinicaltrials.gov database was consulted, and after employing specific exclusion criteria, 11 clinical trials were selected. Nanoparticle albumin-stabilized paclitaxel was evaluated in ten clinical trials and paclitaxel-incorporating polymeric micelles were assessed in one clinical trial. Overall, this review confirmed a clinical benefit in the use of nanoparticle albumin-stabilized paclitaxel for the treatment of breast cancer, with reduced toxicity when compared to first-line treatments. Three studies did not meet the primary endpoint, however, and so the authors advised further evaluations. Although the use of nanomedicine is revolutionizing the cancer field, to integrate this regimen into generalized clinical treatment, additional clinical trials must be performed to achieve a favorable safety and efficacy profile.
- Roots and rhizomes of wild Asparagus: nutritional composition, bioactivity and nanoencapsulation of the most potent extractPublication . Adouni, Khaoula; Júlio, Ana; Santos-Buelga, Celestino; González-Paramás, Ana M.; Filipe, Patrícia; Rijo, Patricia; Costa Lima, Sofia A.; Reis, Salette; Fernandes, Ângela; Ferreira, Isabel C.F.R.; Fernández-Ruiz, Virginia; Morales, Patricia; Flamini, Guido; Achour, Lotfi; Fonte, PedroThe nutritional composition and bioactive properties of roots and rhizomes of Asparagus stipularis were evalu- ated. Antioxidant activity of extracts obtained by infusion was evaluated using free radicals scavenging and reducing power methods. Porcine liver primary cell was used to check the hepatotoxicity of infusions. Results revealed that Asparagus samples are likely a source of nutrients, such as dietary fibre and essential fatty acids. HPLC-DAD-ESI/MS characterization of infusions allowed the identification and quantitation of 7 phenolic compounds, all hydroxycinnamoyl derivatives, with caffeic acid as the most abundant. Roots infusion contained the highest amounts of these compounds. It also exhibited the highest antioxidant activity in all assays, with EC50 values of 0.44 ± 0.01, 0.98 ± 0.03 and 0.64 ± 0.01 mg/mL for DPPH, ABTS and FRAP assays, respectively, with no toxicity towards PLP2 primary cell cultures (GI50 > 400 μg/mL). PLGA nanoparticles loaded with root extract were prepared using solvent-evaporation double emulsion method. Nanoparticles size was about 260 nm and a polydispersity index around 0.1, with a zeta potential of about -36 mV, as well as a good encapsulation efficiency of approximately 83%. Their morphology was analysed by SEM and spherical polymeric nanoparticles with a smooth surface were observed. FTIR and DSC were also performed, which allowed corroborating the efficacy of the encapsulation and to confirm the production of a stable and robust system to load Asparagus extracts. The developed nanoparticles are expected to be used as delivery systems for bioactive compounds of A. stipularis and they could be used as an innovative dietary supplement.