iBB

When an idea in a coffee break in an international meeting turns into a paper, Pedro Fonte from BERG-iBB in collaboration with researchers from UFVJM, Brazil just published a work in JSFA Reports performing an optimization of the brewing parameters on coffee extraction using a central composite rotatable design. The effects of extraction time, particle size of ground coffee, extraction temperature, coffee-to-water ratio, stirring on caffeine yield, and soluble solids on caffeine concentrations were studied. Optimized parameters showed 45 min sufficed to perform a cold extraction at 4°C and 24°C. The parameters selected for validation were 24°C, 30% coffee-to-water ratio, a stirring of 400 rpm resulting in 3.98 mg/ml of extracted caffeine, 11.20 °Brix, and 93.9% of caffeine yield. The smaller particle size (595 μm) displayed the higher caffeine extraction of about 4 mg/ml. This study reveals the high efficiency of cold brew extraction and its potential at the industrial scale, decreasing costs with energy and extraction time, and producing a coffee rich in caffeine and soluble solids.

Wound care is clinically demanding due to treatment inefficiency and represents an economic burden for healthcare systems. A promising therapeutic strategy is the use of exogenous growth factors that are decreased at the wound site and hence limit 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. In a paper published in Materials, Pedro Fonte from BERG-iBB in a collaboration with researchers from CCMAR, University of Algarve and LAQV, University of Porto performed a standing point about a promising strategy to treat different types of wounds by the topical delivery of insulin-loaded nanocarriers.

Encapsulation in the food industry has gained relevant importance, mainly due to its contribution to solve food problems by reducing the loss of nutrients, prolonging the shelf-life, and improving food quality and safety. 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 encapsulation advantages and disadvantages, and microencapsulation techniques used to obtain lipid-based carriers for food ingredients delivery are discussed in a review paper just published in the Journal of Food Engineering by Pedro Fonte from BERG-iBB and colleagues from the Federal University of Valleys of Jequitinhonha and Mucuri, Brazil. 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.

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. In a recent publication in the journal Pharmaceutics, Pedro Fonte from BERG-iBB reviewed the development of polymeric nanoparticles by spray-drying for the delivery of therapeutic proteins 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 its features were also addressed.

The buccal route has been used as alternative for delivery of drugs that undergo first-pass metabolism or are susceptible to pH and enzymatic degradation. However, the drug concentration absorbed in the buccal mucosa is often low. The encapsulation of drugs into nanoparticles is an important strategy to improve their buccal delivery. In a recently published review paper in Journal of Controlled Release, Ana Macedo, Pedro Fonte (BERG-iBB) and colleagues overview the nanotechnological approaches developed so far to improve the buccal delivery of drugs. Several types of delivery strategies are addressed and a special focus is placed on pipeline products.

A new strategy to modify cellulose with the short antimicrobial hexapeptide MP196 (RWRWRW-NH2) is proposed by BERG and BSIRG researchers that uses fusions of Cys-terminated derivatives of MP196 and a carbohydrate binding module (CBM). CBM3-MP196-modified cellulose hydrogels displayed antibacterial activity that was significantly higher when compared with controls. This versatile concept offers a toolbox for the functionalization of different cellulose materials with a broad choice in peptides. the paper was published in Acta Biomaterialia. The work was funded by project CBM-X.

Many studies that apply PnD in pre-clinical cutaneous wound healing models show large variations in the choice of the animal species (e.g., large animals, rodents), the choice of diabetic or non-diabetic animals, the type of injury (full-thickness wounds, burns, radiation-induced wounds, skin flaps), the source and type of PnD (placenta, umbilical cord, fetal membranes, cells, secretomes, tissue extracts), the method of administration (topical application, intradermal/subcutaneous injection, intravenous or intraperitoneal injection, subcutaneous implantation), and the type of delivery systems (e.g., hydrogels, synthetic or natural biomaterials as carriers for transplanted cells, extracts or secretomes). In a collaborative work coordinated by Prof. Pedro Fonte under the COST Action SPRINT (CA17116), the Postdoc researcher Ana Macedo and Master student Francisca Mendes from BERG-iBB, provided a comprehensive and integrative overview of the application of PnD in wound healing to assess its efficacy in preclinical animal models. The review was published in Frontiers in Bioengineering and Biotechnology.

The nutritional composition and bioactive properties of roots and rhizomes of Asparagus stipularis were evaluated to demonstrate its potential in the food and pharmaceutical industries. HPLC-DAD-ESI/MS characterization of infusions allowed the identification and quantitation of 7 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). The extract was encapsulated into PLGA nanoparticles obtaining a size of 260 nm and a polydispersity index around 0.1, with a zeta potential of -36 mV, as well as a good encapsulation efficiency of approximately 83%. The particles had a spherical morphology and smooth surface. FTIR and DSC assays confirmed the efficacy of the encapsulation methodology. This paper was published in Food Bioscience by Pedro Fonte from BERG-iBB in a transnational collaboration with researchers from Portugal, Spain, Italy and Tunisia. The developed systems will be used as delivery systems for bioactive compounds of A. stipularis and as an innovative dietary supplement.

Alzheimer’s disease (AD) is a progressive and irreversible brain disorder that hampers memory and thinking, affects the capacity to perform daily tasks, and leads 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 an alternative to deliver drugs and improve treatment of AD.  In a paper published in Drug Delivery and Translational Research, Pedro Fonte from BERG-iBB performed an overview on the strategies for drug intranasal delivery for AD treatment. In the paper, the advantages and disadvantages of the nasal route and the delivery systems developed so far are discussed. A special focus is given to the use of permeation enhancers, the types of intranasal drug delivery devices, as well as possible toxicity concerns.

Quinic acid (QA) is a cyclic polyol exhibiting anticancer properties on several cancers. However, the potential role of QA derivatives against glioblastoma is not well established. Pedro Fonte from BERG-IBB in a joint collaboration with Tampere University, Lady Doak College, University of Aveiro, Faculty of Pharmacy-University of Lisbon, and the Institute for Systems Biology proposed a new strategy for quinic acid delivery for glioblastoma treatment in a recent publication in Future Medicinal Chemistry. Sixteen novel QA derivatives and QA-16 encapsulated poly (lactic-co-glycolic acid) nanoparticles (QA-16-NPs) were screened for their anti-glioblastoma effect. The presence of a tertiary hydroxy and silylether groups in the lead compound were identified for the antitumor activity. QA-16 displayed 90% inhibition with the IC50 of 10.66 μM and 28.22 μM for LN229 and SNB19, respectively. The induction of apoptosis is faster with the increased fold change of caspase 3/7 and reactive oxygen species. Overall, it was observed the QA-16 and QA-16-NPs shows similar cytotoxicity effect, providing the opportunity to use QA-16 as a potential chemotherapeutic agent.

Poly-ɛ-caprolactone (PCL) is a biodegradable polyester that has FDA and CE approval as a medical device. Despite PCL-based NPs being widely studied in the biomedical field for their advantages as controlled drug delivery systems, little data describe PCL NPs’ toxicity, particularly immunotoxicity. In a recent publication in the journal Chemical Research in Toxicology,  Pedro Fonte from BERG-iBB in collaboration with colleagues from the Center for Neuroscience and Cell Biology, University of Coimbra describe the safe-by-design development of nanoparticles for nanomedicine applications. It was concluded that generalizations among different PCL NP delivery systems must be avoided, and that immunotoxicity assessments should be performed in the early stage of product development to increase the clinical success of the nanomedicine.