Browsing by Author "Bessa, Lucinda"
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- Dual-action peptides as potential novel topical agents for treatment of skin and soft tissue infectionsPublication . Gomes, Ana; Bessa, Lucinda; Ferraz, Ricardo; Prudêncio, Cristina; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaChronic skin and soft-tissue infections (SSTI) such as diabetic foot ulcers (DFU) exhibit signs and symptoms that are consistent with localized bacterial biofilms that contribute to tissue destruction, delayed woundhealing and other serious complications. As such, most current approaches for advanced wound care aim at providing antimicrobial protection to the open wound together with a matrix scaffold (often collagenbased) to boost reestablishment of the skin tissue. While efficient production of recombinant human collagen remains an unmet goal, an alternative sensible option may be the design of formulations containing collagen-boosting instead of collagen-like components. Actually, collagen-boosting peptides, e.g., Matrikines®, are already used in cosmetics to promote extracellular matrix production, rebuilding structure and restoring all functions of healthy skin. Additionally, many antimicrobial peptides (AMP) can also act as wound-healing peptides, thus displaying the dual antimicrobial and tissue-regenerating properties highly desired in novel topical agents for treatment of SSTI. With the increasing prevalence of multi-drug resistant bacteria, and considering the burden that DFU alone represents to human health and healthcare facilities, the development of novel topical agents for effective treatment for this and other severe SSTI is an urgent need.
- 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.