Percorrer por autor "Fernandes, Iva"
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- Boosting cosmeceutical peptides: coupling imidazolium-based ionic liquids to pentapeptide-4 originates new leads with antimicrobial and collagenesis-inducing activitiesPublication . Gomes, Ana; Bessa, Lucinda J.; Fernandes, Iva; Aguiar, Luísa; Ferraz, Ricardo; Monteiro, Cláudia; Martins, M. Cristina L.; Mateus, Nuno; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaFollowing our previous reports on dual-action antibacterial and collagenesis-inducing hybrid peptide constructs based on “pentapeptide-4” (PP4, with amino acid sequence KTTKS), whose N-palmitoyl derivative is the well-known cosmeceutical ingredient Matrixyl, herein we disclose novel ionic liquid/PP4 conjugates (IL-KTTKS). These conjugates present potent activity against either antibiotic-susceptible strains or multidrug resistant clinical isolates of both Gram-positive and Gram-negative bacterial species belonging to the so-called “ESKAPE” group of pathogens. Noteworthy, their antibacterial activity is preserved in simulated wound fluid, which anticipates an effective action in the setting of a real wound bed. Moreover, their collagenesis-inducing effects in vitro are comparable to or stronger than those of Matrixyl. Altogether, IL-KTTKS exert a triple antibacterial, antifungal, and collagenesis-inducing action in vitro. These findings provide solid grounds for us to advance IL-KTTKS conjugates as promising leads for future development of topical treatments for complicated skin and soft tissue infections (cSSTI). Further studies are envisaged to incorporate IL-conjugates into suitable nanoformulations, to reduce toxicity and/or improve resistance to proteolytic degradation.
- “Clicking” an ionic liquid to a potent antimicrobial peptide: on the route towards improved stabilityPublication . Gomes, Ana; Bessa, Lucinda J.; Correia, Patrícia; Fernandes, Iva; Ferraz, Ricardo; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaA covalent conjugate between an antibacterial ionic liquid and an antimicrobial peptide was produced via “click” chemistry, and found to retain the parent peptide’s activity against multidrug-resistant clinical isolates of Gram-negative bacteria, and antibiofilm action on a resistant clinical isolate of Klebsiella pneumoniae, while exhibiting much improved stability towards tyrosinase-mediated modifications. This unprecedented communication is a prelude for the promise held by ionic liquids -based approaches as tools to improve the action of bioactive peptides.
- Disclosure of a promising lead to tackle complicated skin and skin structure infections: antimicrobial and antibiofilm actions of peptide PP4-3.1Publication . Gomes, Ana; Bessa, Lucinda J.; Fernandes, Iva; Ferraz, Ricardo; Monteiro, Cláudia; Martins, M. Cristina L.; Mateus, Nuno; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaEfficient antibiotics are being exhausted, which compromises the treatment of infections, including complicated skin and skin structure infections (cSSTI) often associated with multidrug resistant (MDR) bacteria, methicillin-resistant S. aureus (MRSA) being the most prevalent. Antimicrobial peptides (AMP) are being increasingly regarded as the new hope for the post-antibiotic era. Thus, future management of cSSTI may include use of peptides that, on the one hand, behave as AMP and, on the other, are able to promote fast and correct skin rebuilding. As such, we combined the well-known cosmeceutical pentapeptide-4 (PP4), devoid of antimicrobial action but possessing collagenesis-boosting properties, with the AMP 3.1, to afford the chimeric peptide PP4-3.1. We further produced its N-methyl imidazole derivative, MeIm-PP4-3.1. Both peptide-based constructs were evaluated in vitro against Gram-negative bacteria, Gram-positive bacteria, and Candida spp. fungi. Additionally, the antibiofilm activity, the toxicity to human keratinocytes, and the activity against S. aureus in simulated wound fluid (SWF) were assessed. The chimeric peptide PP4-3.1 stood out for its potent activity against Gram-positive and Gram-negative bacteria, including against MDR clinical isolates (0.8 ≤ MIC ≤ 5.7 µM), both in planktonic form and in biofilm matrix. The peptide was also active against three clinically relevant species of Candida fungi, with an overall performance superior to that of fluconazole. Altogether, data reveal that PP4-3.1 is as a promising lead for the future development of new topical treatments for severe skin infections.
- Infusions and decoctions of dehydrated fruits of Actinidia arguta and Actinidia deliciosa: Bioactivity, radical scavenging activity and effects on cells viabilityPublication . Silva, Ana Margarida; Pinto, Diana; Fernandes, Iva; Albuquerque, Tânia Gonçalves; Costa, Helena S.; Freitas, Vitor; Rodrigues, Francisca; Oliveira, M. Beatriz P.P.Actinidia deliciosa and A. arguta fruits (kiwifruit and kiwiberry, respectively) are an excellent source of bioactive compounds. The aim of this paper is to valorize the fruits that are not commercialized (e.g. due to inadequate size or physical damage) in infusions and decoctions. The antioxidant activity, the scavenging activity against reactive species, the phenolic profile and the intestinal effects of infusions and decoctions of dehydrated fruits were evaluated and compared. Decoctions presented the highest antioxidant activity and a good ability to capture HOCl and NO. The phenolic composition of A. arguta present quinic acid, cis-caftaric acid and its derivatives, caffeoyl hexoside, luteolin glucuronide, quercetin derivatives and myristin, while A. deliciosa extracts were characterized by the presence of quinic acid, caffeic acid and its derivatives and caffeoyl hexoside. No adverse effects were observed on Caco-2 and HT29-MTX cells. Kiwiberry decoctions showed to be the best option to keep the fruits benefits.
- Insights into the development of grapefruit nutraceutical powder by spray drying: physical characterization, chemical composition and 3D intestinal permeabilityPublication . González, Freddy; García‐Martínez, Eva; Camacho, María; Martínez‐Navarrete, Nuria; Sarmento, Bruno; Fernandes, Iva; Freitas, Victor; Rodrigues, Francisca; Oliveira, BeatrizThe development of functional and nutraceutical foods comes from a greater awareness of the relationship between food and health by consumers. In recent years, the idea of purifying and encapsulating bioactive compounds through techniques such as spray drying has been well received by the food industry. The development and characterization of a grapefruit (Citrus paradisi) nutraceutical powder obtained by spray drying is of great interest owing to the different bioactive compounds and the potential health effects.
- Peptide conjugates for the topical treatment of infected woundsPublication . Gomes, Ana; Fernandes, Iva; Bessa, Lucinda; Ferreira, Mariana; Maciel, Joana; Plácido, Alexandra; Teixeira, Cátia; Leal, Ermelindo; Ferraz, Ricardo; Gameiro, Paula; Carvalho, Eugénia; Gomes, PaulaDue to widespread multidrug-resistant (MDR) microbes, efficient treatments for infected wounds are being exhausted.1 The symptoms of wound infection are consistent with local polymicrobial biofilms, which are difficult to eliminate and delay the healing process. The current standard of care requires oral antibiotics and other measures, often complex and distressing (e.g., amputations). A perfect treatment should promote both antimicrobial protection and fast tissue regeneration, to improve the inefficient healing in elderly people affected with, e.g., diabetes or venous/arterial insufficiency. 2 Considering the above, we advance peptide conjugates as potential active pharmaceutical ingredients for topical formulations to tackle skin infections. Such conjugates are anticipated to concomitantly display antimicrobial and anti-biofilm action along with fast healing through, e.g., collagenesis-inducing effects. Promising results were obtained with chimeric peptides combining a de novo designed antimicrobial peptide sequence 3 with a cosmetic peptide, used as anti-aging, with ability to induce collagen production.4 The best constructs exhibited: (i) antibacterial and anti-biofilm activity against Gram-positive and Gram-negative bacteria, including MDR clinical isolates; (iii) improved action against S. aureus (prevalent pathogen in chronically-infected wounds) in simulated wound fluid; and (v) antifungal activity. 5 The replacement of the antimicrobial peptide by an ionic liquid afforded a new conjugate, a peptide-ionic liquid construct, with broadspectrum antibacterial activity, antifungal action, and collagen-inducing effect. These results will be shown alongside the most recent findings that provide deeper insight into the mode of action of the best conjugates.
- Peptide-ionic liquid conjugates towards the treatment of skin infectionsPublication . Gomes, Ana; Bessa, Lucinda; Fernandes, Iva; Teixeira, Cátia; Aguiar, Luísa; Ferraz, Ricardo; Monteiro, Cláudia; Martins, Cristina; Mateus, Nuno; Gameiro, Paula; Gomes, PaulaThe treatment of complicated skin infections, like diabetic foot ulcers and other chronic wounds, are often associated with persistent polymicrobial biofilms that delay and difficult the healing process. The most severe cases culminate in inpatient hospital admission, where infections can be exacerbated by hospital-acquired pathogens, in particular, if caused by the so-called ESKAPE pathogens, for which few efficient antibiotics are available. The current biomedical approaches to chronic wounds aim at providing both protection against multidrug-resistant (MDR) bacteria and a matrix scaffold, often collagen-based, to boost the reestablishment of healthy skin. Therefore, new options and new antibiotics are urgently needed and having that in mind our strategy is to use: i) antimicrobial peptides (AMP) to prevent or treat infection in the open wound; ii) collagen-inducing peptides (CBP) to induce fast healing; iii) and ionic liquids (IL) with intrinsic antimicrobial chemical permeation enhancement properties for an improved skin permeation. Through different combinations of these three types of building blocks, we aim to find a new class of active pharmaceutical ingredients suitable for topical application in the treatment of complicated skin infections. All the different conjugates designed and tested in vitro thus far will be presented. The most promising ones result from conjugation of CBP with IL, delivering a new type of conjugate with potent antibacterial, antifungal, and collagen-inducing effects on human dermal fibroblasts. Hence, these peptide-ionic liquid conjugates are promising leads towards the development of a topical formulation for the treatment of complicated skin infections.
- Peptide/ionic liquid conjugates to tackle complicated skin infections: antimicrobial, antibiofilmand collagen-boosting effectsPublication . Gomes, Ana; Bessa, Lucinda; Fernandes, Iva; Aguiar, Luisa; Ferraz, Ricardo; Monteiro, Cláudia; Martins, Cristina; Mateus, Nuno; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaComplicated skin and soft tissue infections (cSSTI) like, e.g., diabeticfoot ulcers (DFU), are severe cases of cutaneous and deeper soft tis-sue infections. Their symptoms are consistent with local polymicro-bial biofilms, which are difficult to eliminate and delay the healing process. The standard-of-care for cSSTI requires oral antibiotics andother measures, often complex and distressing (e.g., amputations). Due to widespread multidrug resistant (MDR) microbes, efficient treatments for cSSTI are being exhausted. These should promote both antimicrobial protection and fast tissue regeneration, to at one the inefficient healing in elderly people afflicted with, e.g., diabetes orvenous/arterial insufficiency.
- Turning a Collagenesis-Inducing Peptide Into a Potent Antibacterial and Antibiofilm Agent Against Multidrug-Resistant Gram-Negative BacteriaPublication . Gomes, Ana; Bessa, Lucinda J.; Fernandes, Iva; Ferraz, Ricardo; Mateus, Nuno; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaAntimicrobial resistance is becoming one the most serious health threats worldwide, as it not only hampers effective treatment of infectious diseases using current antibiotics, but also increases the risks of medical procedures like surgery, transplantation, bone and dental implantation, chemotherapy, or chronic wound management. To date, there are no effective measures to tackle life-threatening nosocomial infections caused by multidrug resistant bacterial species, of which Gram-negative species within the so-called "ESKAPE" pathogens are the most worrisome. Many such bacteria are frequently isolated from severely infected skin lesions such as diabetic foot ulcers (DFU). In this connection, we are pursuing new peptide constructs encompassing antimicrobial and collagenesis-inducing motifs, to tackle skin and soft tissue infections by exerting a dual effect: antimicrobial protection and faster healing of the wound. This produced peptide 3.1-PP4 showed MIC values as low as 1.0 and 2.1 μM against Escherichia coli and Pseudomonas aeruginosa, respectively, and low toxicity to HFF-1 human fibroblasts. Remarkably, the peptide was also potent against multidrug-resistant isolates of Klebsiella pneumoniae, E. coli, and P. aeruginosa (MIC values between 0.5 and 4.1 μM), and hampered the formation of/disaggregated K. pneumoniae biofilms of resistant clinical isolates. Moreover, this notable hybrid peptide retained the collagenesis-inducing behavior of the reference cosmeceutical peptide C16-PP4 ("Matrixyl"). In conclusion, 3.1-PP4 is a highly promising lead toward development of a topical treatment for severely infected skin injuries.