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- Intranasal drug delivery for treatment of Alzheimer's diseasePublication . Fonseca, Leonor Cancela; Lopes, Joao; Vieira, Joao; Viegas, Claudia; Oliveira, Claudia S.; Hartmann, Rafael P.; Fonte, PedroThe Alzheimer's disease is a neurodegenerative condition with severe consequences interfering with patient quality of life. It is characterized as a progressive and irreversible brain disorder hampering memory and thinking, affecting the capacity to perform daily tasks leading to physical and cognitive incapacitation. The conventional treatment occurs by the oral route, but it presents relevant drawbacks such as low bioavailability, fast metabolism, limited brain exposure, and undesirable side effects. The intranasal route has been proposed as a promising alternative to deliver drugs and improve the Alzheimer's disease treatment. Still, there is not a clear alternative delivery system available in the market with advantageous bioavailability and safety. The aim of this review is to perform an overview on the strategies for drug intranasal delivery for Alzheimer's disease treatment. The advantages and disadvantages of this delivery route and the delivery systems developed so far are discussed. A special focus is given on the use of permeation enhancers, the types of intranasal drug delivery devices, as well as possible toxicity concerns.
- 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.
- An insight on lipid nanoparticles for therapeutic proteins deliveryPublication . Viegas, Cláudia; Seck, Fatumata; Fonte, PedroTherapeutic proteins are well-tolerated bioactive compounds used in different therapies, due to its high speci-ficity and biopotency. Nevertheless, they may also present some physicochemical instability, leading to loss of bioactivity hampering treatments. This can be avoided by its loading into lipid nanoparticles, which are biocompatible and biodegradable carriers. The use of lipids nanoparticles to deliver therapeutic proteins over-comes different challenges, allowing its administration by all delivery routes. Thus, therapeutic proteins may be loaded into liposomes, the first developed lipid-based nanocarriers composed of phospholipid bilayers, solid lipid nanoparticles composed of a solid lipid matrix, or nanostructured lipid carriers made of a blend of liquid and solid lipid as matrix. The latter are currently marking the trend in lipid nanocarriers due to its high loading capacity, good stability upon storage and better sustained release pattern. Production methods must focus both on attaining the desired nanocarrier features, and maintenance of therapeutic proteins structure and bioactivity. This review aims to make an insight overview on the application of lipid nanoparticles to deliver therapeutic proteins, showing its potential in different therapies. A special focus is given to the production techniques to obtain therapeutic proteins-loaded lipid nanoparticles.
- 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.
- 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.
- Pluronic® triblock copolymer-based nanoformulations for cancer therapy: A 10-year overviewPublication . de Castro, Karine Cappuccio; Coco, Julia Cedran; dos Santos, Érica Mendes; Ataide, Janaína Artem; Martinez, Renata Miliani; do Nascimento, Mônica Helena Monteiro; Prata, João; Fonte, Pedro; Severino, Patrícia; Mazzola, Priscila Gava; Baby, André Rolim; Souto, Eliana Barbosa; de Araujo, Daniele Ribeiro; Lopes, André MoreniThis paper provides a review of the literature on the use of Pluronic (R) triblock copolymers for drug encapsulation over the last 10 years. A special focus is given to the progress of drug delivery systems (e.g., micelles, liposomes, micro/nanoemulsions, hydrogels and nanogels, and polymersomes and niosomes); the beneficial aspects of Pluronic (R) triblock copolymers as biological response modifiers and as pharmaceutical additives, adjuvants, and stabilizers, are also discussed. The advantages and limitations encountered in developing site-specific targeting approaches based on Pluronic-based nanostructures in cancer treatment are highlighted, in addition to inno-vative examples for improving tumor cytotoxicity while reducing side effects.
- A brief overview of the oral delivery of insulin as an alternative to the parenteral deliveryPublication . Macedo, Ana; Filipe, Patricia; Thome, Natalia G.; Vieira, Joao; Oliveira, Carolina; Teodosio, Catarina; Ferreira, Raquel; Roque, Luis; Fonte, PedroDiabetes mellitus greatly affects the quality of life of patients and has a worldwide prevalence. Insulin is the most commonly used drug to treat diabetic patients and is usually administered through the subcutaneous route. However, this route of administration is ineffective due to the low concentration of insulin at the site of action. This route of administration causes discomfort to the patient and increases the risk of infection due to skin barrier disturbance caused by the needle. The oral administration of insulin has been proposed to surpass the disadvantages of subcutaneous administration. In this review, we give an overview of the strategies to deliver insulin by the oral route, from insulin conjugation to encapsulation into nanoparticles. These strategies are still under development to attain efficacy and effectiveness that are expected to be achieved in the near future.
- 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.
- 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.
- Lipid-based carriers for food ingredients deliveryPublication . Barroso, Livia; Viegas, Cláudia; Vieira, Joao; Ferreira-Pego, Cintia; Costa, Joyce; Fonte, PedroThe encapsulation in the food industry has gained relevant importance, mainly due to its contribution to solve food problems by reducing the loss of nutrients, prolong the shelf-life, and improve food quality and safety. The lipid-based delivery systems as microemulsions, liposomes, solid lipid nanoparticles and nanostructured lipid carriers are widely used to deliver food ingredients due to their ability to protect and deliver it, enhancing its functionality and bioavailability. Despite the benefits on delivering food ingredients the toxicity profile of such carriers is usually neglected. The aim of this review is to provide a detailed overview on the application of lipid-based carriers to deliver food ingredients. Herein, the encapsulation advantages and disadvantages, and microencapsulation techniques used to obtain lipid-based carriers are discussed. More importantly, the different types of lipid-based carriers used for food ingredients delivery are thoroughly scrutinized, as well as their application in foods and possible toxicity concerns.
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