Browsing by Author "Macedo, Ana S."
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- Advances in Pancreatic Cancer treatment by Nano-Based drug delivery systemsPublication . Viegas, Cláudia; Patrício, Ana B.; Prata, João; Fonseca, Leonor; Macedo, Ana S.; Duarte, Sofia O. D.; Fonte, PedroPancreatic cancer represents one of the most lethal cancer types worldwide, with a 5-year survival rate of less than 5%. Due to the inability to diagnose it promptly and the lack of efficacy of existing treatments, research and development of innovative therapies and new diagnostics are crucial to increase the survival rate and decrease mortality. Nanomedicine has been gaining importance as an innovative approach for drug delivery and diagnosis, opening new horizons through the implementation of smart nanocarrier systems, which can deliver drugs to the specific tissue or organ at an optimal concentration, enhancing treatment efficacy and reducing systemic toxicity. Varied materials such as lipids, polymers, and inorganic materials have been used to obtain nanoparticles and develop innovative drug delivery systems for pancreatic cancer treatment. In this review, it is discussed the main scientific advances in pancreatic cancer treatment by nano-based drug delivery systems. The advantages and disadvantages of such delivery systems in pancreatic cancer treatment are also addressed. More importantly, the different types of nanocarriers and therapeutic strategies developed so far are scrutinized.
- An overview on spray-drying of protein-loaded polymeric nanoparticles for dry powder inhalationPublication . Marante, Tânia; Viegas, Cláudia Sofia; Duarte, Inês; Macedo, Ana S.; Fonte, PedroThe delivery of therapeutic proteins remains a challenge, despite recent technological advances. While the delivery of proteins to the lungs is the gold standard for topical and systemic therapy through the lungs, the issue still exists. While pulmonary delivery is highly attractive due to its non-invasive nature, large surface area, possibility of topical and systemic administration, and rapid absorption circumventing the first-pass effect, the absorption of therapeutic proteins is still ineffective, largely due to the immunological and physicochemical barriers of the lungs. Most studies using spray-drying for the nanoencapsulation of drugs focus on the delivery of conventional drugs, which are less susceptible to bioactivity loss, compared to proteins. Herein, the development of polymeric nanoparticles by spray-drying for the delivery of therapeutic proteins is reviewed with an emphasis on its advantages and challenges, and the techniques to evaluate their in vitro and in vivo performance. The protein stability within the carrier and the features of the carrier are properly addressed.
- Design and synthesis of novel quinic acid derivatives: in vitro cytotoxicity and anticancer effect on glioblastomaPublication . Murugesan, Akshaya; Holmstedt, Suvi; Brown, Kenna C.; Koivuporras, Alisa; Macedo, Ana S.; Nguyen, Nga; Fonte, Pedro; Rijo, Patricia; Yli-Harja, Olli; Candeias, Nuno R.; Kandhavelu, MeenakshisundaramAim: Quinic acid (QA) is a cyclic polyol exhibiting anticancer properties on several cancers. However, potential role of QA-derivatives against glioblastoma is not well established. Methodology & results: Sixteen novel QA-derivatives and QA-16 encapsulated poly (lactic-co-glycolic acid) nanoparticles (QA-16-NPs) were screened for their anti-glioblastoma effect using standard cell and molecular biology methods. Presence of a tertiary hydroxy and silylether groups in the lead compound were identified for the antitumor activity. QA-16 have 90% inhibition with the IC50 of 10.66 mu M and 28.22 mu M for LN229 and SNB19, respectively. The induction of apoptosis is faster with the increased fold change of caspase 3/7 and reactive oxygen species. Conclusion: QA-16 and QA-16-NPs shows similar cytotoxicity effect, providing opportunity to use QA-16 as a potential chemotherapeutic agent.
- 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.
- Fusions of a carbohydrate binding module with the small cationic hexapeptide RWRWRW confer antimicrobial properties to cellulose-based materialsPublication . Barbosa, Mariana; Simões, Hélvio; Pinto, Sandra N.; Macedo, Ana S.; Fonte, Pedro; Prazeres, D.Miguel F.The emergence of antibiotic-resistant bacteria is a critical worldwide healthcare problem. In the specific case of wound care, new and effective alternatives to currently available solutions are urgently needed. Cellulose-based dressings, for example, could be made more attractive if rendered antimicrobial. This work proposes a new strategy to modify cellulose-based materials with the short antimicrobial hexapeptide MP196 (RWRWRW - NH 2 ) that relies on a biomolecular recognition approach based on carbohydrate binding modules (CBMs). Specifically, we focused on the modification of hydrogels, paper, and microfibrillated cellulose (MFC) with fusions of the CBM3 from Clostridium thermocellum ( C. thermocellum ) with derivatives of MP196. The fusions are prepared by promoting the formation of a disulfide bond between Cys-terminated derivatives of MP196 and a CBM3 that is pre-anchored in the materials. The CBM3MP196-modified materials displayed antibacterial activity against Escherichia coli ( E. coli ), Pseudomonas aeruginosa ( P. aeruginosa ) and Staphylococcus aureus ( S. aureus ) that was significantly higher when compared with the activity of materials prepared by physical adsorption of MP196. The biomolecular strategy provides a more favorable orientation, exposure, and distancing of the peptide from the matrix. This versatile concept provides a toolbox for the functionalization of cellulose materials of different origins and architectures with a broad choice in peptides. Functionalization under mild biological conditions avoids further purification steps, allowing for translational research and multiple applications as drug delivery systems, scaffolds for tissue engineering and biomaterials.
- Impact of the use of cryoprotectants in the production of freeze-dried soluble coffee from cold brew arabica coffeePublication . Barroso, Livia Alves; Viegas, Cláudia; Stančiauskaitė, Monika; Macedo, Ana S.; Lemos, Iara Lopes; da Costa, Joyce Maria Gomes; Schmiele, Marcio; da Silveira, João Vinícios Wirbitzki; Brandão, Pedro; Amaral, Tatiana Nunes; Fonte, PedroCold brew is a method of coffee extraction that uses low temperature, preserving the volatile compounds of coffee. Freeze-drying allows the preservation of coffee features and nutritional value. The aim of this study was to evaluate the effects of different cryoprotectants in cold brew extracts as a basis for freeze-dried coffee production. Thus, the Coffea arabica extracts and the soluble coffee were characterized concerning caffeine content, antioxidant capacity, total phenolic compounds, and antimicrobial activity to verify the potential of this method. The extracts did not show antimicrobial activity with a high soluble solid content. It was observed that the cold extraction methods were efficient regarding the caffeine content, antioxidant capacity, and total phenolic compounds. Freeze-dried coffees also did not show antimicrobial activity, and they maintained the water and humidity activity standards. In general, cryoprotectants displayed an unfavorable influence on the extract and freeze-dried coffee in the analyses performed. The coffee extract without cryoprotectants had a higher antioxidant capacity (88.12%) and content of phenolic compounds (7.74 mg AG/mL of the coffee extract). Only for the analyses of soluble solids, the cryoprotectants mannitol and fructose showed promising results (14.03 degrees Brix, 14.40 degrees Brix, 11.33 degrees Brix, respectively). Thus, for the analyses conducted, the cryoprotectants did not lead to significant advantages for this process.
- 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.