Browsing by Author "Ribeiro, I. A."
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- Characterization of a novel 3D-polymeric scaffold as a co-delivery systemPublication . Zegre, Miguel; Silveira, M.; Anjos, I.; Ribeiro, I. A.; Santos, C.; Caetano, Liliana Aranha; Gonçalves, L.; Bettercourt, A.Osteomyelitis is an inflammation of the bone caused by infection, leading to necrosis and tissue destruction. It can cause persistent morbidity and become a chronic disease, being one of the infectious diseases most difficult to manage. Staphylococcus aureus is the most usual causative pathogen in osteomyelitis, and bacterial infections are often complicated by concomitant fungal infections, Candida sp. being the most common. Co-encapsulation of drugs provides a convenient means for the administration of multiple drugs directed at commonly associated diseases. Three-dimensional scaffolds have become a crucial element of bone tissue engineering and regenerative medicine, are designed to provide an ideal environment for bone formation. Thus, this work aims to develop a new local drug-delivery system for the modulation of polymicrobial activity in bone infections, through the co-delivery of minocycline and voriconazole to the local site of infection, while fostering bone repair.
- Chitosan nanoparticles loaded with minocycline targeting osteomyelitisPublication . Zegre, Miguel; Bastron, S.; Ribeiro, I. A.; Caetano, Liliana Aranha; Gonçalves, L.; Bettencourt, A.Effective control of osteomyelitis (bone infection) with reduced toxicity is a current challenge. Targeted and controlled drug delivery systems allow: decreased toxicity, upgraded drug targeting, and improved therapeutic effect. Strategy: a) Innovative chitosan nanoparticulate system: nanoparticles loaded with minocycline (antibacterial), and alternative as a local delivery system; b) Nanoparticles and biofilms: advantages: enhanced bioavailability, targeted delivery of antibiotics magnification, local release of antibiotics, controlled and sustained release, and protection against deactivating enzymes.
- Chitosan-based nanoparticles as a dual drug delivery system directed to bone infection therapyPublication . Falcão, J.; Zegre, Miguel; Bastron, S.; Ribeiro, I. A.; Gonçalves, L.; Bettencourt, A.Osteomyelitis treatment is usually described as a challenging issue, mainly because of the necessity of high levels of antimicrobials employed for extended periods, since the infection is characterized by poor blood circulation. Innovative options of targeted and controlled drug delivery systems, presenting sustained antimicrobial release, high concentrations of drugs in the infected areas, low concentrations in the bloodstream, and promotion of osteogenesis, need to be considered.
- Co-delivery of antimicrobials based on poly(D,L-lactic acid) 3D-scaffoldsPublication . Zegre, Miguel; Falcão, M.; Ribeiro, I. A.; Santos, C.; Barros, J.; Monteiro, F. J.; Ferraz, M. P.; Caetano, Liliana Aranha; Gonçalves, L.; Bettencourt, A.Bone infection treatment is a clinical challenge, often complicated by simultaneous polymicrobial infections. A growing number of studies address the co-isolation of fungal and bacterial species, such as Candida albicans and Staphylococcus aureus, from polymicrobial biofilm associated with osteomyelitis. Recent publications demonstrate that scaffolds with local drug delivery ability, display high antimicrobial efficiency rates and reduced toxicity, suppressing the progression of bone disease and decreasing the number of pathogens in mono- or polymicrobial-biofilms.
- Poly(D,L-lactic acid) scaffolds as an innovative approach to the treatment of mixed S. aureus-C. albicans biofilmsPublication . Zegre, Miguel; Barros, J.; Ribeiro, I. A.; Santos, C.; Aranha Caetano, Liliana; Gonçalves, L.; Monteiro, F.; Ferraz, M.; Bettencourt, A.Introduction: The treatment of bacterial joint and bone infections in patients after multiple revision arthroplasties is very challenging. An expanding number of studies report the co-isolation of fungal and bacterial species (such as Candida albicans and Staphylococcus aureus) from polymicrobial biofilm associated with infections related to bone infections. Current investigations establish that local-specific drug delivery scaffolds with low toxicity and increased efficiency to specific sites when compared to oral and systemic administration approaches, can considerably lower the number of viable microorganisms in polymicrobial biofilms, preventing simultaneously the progression of infection in bone disorder. Notably, the development of co-delivery systems of at least two antimicrobials is yet a neglected approach, while it may be a critical strategy for the treatment of infections associated with polymicrobial biofilms. Simultaneously, it is recommended to assess the contribution of each microbial population within the biofilm to select the best therapy to treat polymicrobial infections. Among different biomaterials used in scaffolds as drug-delivery carriers, poly(lactic acid) (PLA) based polymers are being widely studied due to their versatility, low toxicity, and tailored biodegradability having the US Food and Drug Administration approval for clinical use. The adequate osteoconductive and anti-S. aureus effects of a collagen functionalized poly(D, L-lactic acid) (PDLLA) porous scaffold loaded with minocycline (a tetracycline antibiotic) have been previously demonstrated3. In the present study, we focus on the problem of mixed bacterial-fungal biofilm infections and the joining of two antimicrobials in the PDLLA scaffold. Minocycline and voriconazole (an antifungal triazole) were the chosen model drugs, since minocycline may represent a promising drug that can be administered in combination with azoles (namely voriconazole) to treat infections caused by pathogenic Candida species. Morphological and chemical properties of the co-delivery PDLLA scaffolds, as well as drug release profiles, were examined. The antibiofilm activity of these drug delivery systems was tested against single- and dual-species biofilms of S. aureus and C. albicans. The formation of dual-species S. aureus – C. albicans biofilms was studied over time to understand the relationship between both microorganisms during in vitro biofilm formation. Cytocompatibility and osteoconductive tests were also conducted using MG-63 osteoblasts to assess the biocompatibility of the PDLLA scaffolds.
- Poly(D,L-lactic acid) scaffolds as an innovative approach to the treatment of mixed S. aureus-C. albicans biofilmsPublication . Zegre, Miguel; Barros, J.; Ribeiro, I. A.; Santos, C.; Aranha Caetano, Liliana; Gonçalves, L.; Monteiro, F.; Ferraz, M.; Bettencourt, A.Problem - Bone infections associated with polymicrobial biofilm formation; mixed bacterial-fungal biofilm infection; Staphylococcus aureus and Candida albicans most described microbials. Strategy - Local drug delivery scaffolds; development of poly-DL-lactic acid (PDLLA) scaffolds; co-delivery of antibacterial and antifungal drugs; minocycline and voriconazole as model drugs.
- Poly(DL-lactic acid) scaffolds adsorbed with minocycline and voriconazole: a new pathway towards infection containmentPublication . Zegre, Miguel; Henriques, M.; Santos, C.; Ribeiro, I. A.; Caetano, Liliana Aranha; Gonçalves, Lídia M.; Bettencourt, Ana F.Bone infection (osteomyelitis): burden as a clinical complication of orthopedic surgeries. Controlled antimicrobial release systems: treat and prevent osteomyelitis. Biomaterials based on porous scaffolds: local administration of high concentration of drugs; no systemic toxicity; extended time. Scaffolds in bone tissue engineering: a combination of bioresorbable polymers with bioactive bioglasses; present biodegradability and biosafety; suitable microenvironment and structure; favor osteogenic differentiation and cell growth. Co-encapsulation of drugs: advantageous means for administration of drugs; novel strategy directed to the co-delivery of two antimicrobials (voriconazole and minocycline).
- Poly(DL-lactic acid) scaffolds as a bone targeting platform for the co-delivery of antimicrobial agents against S. aureus-C.albicans mixed biofilmsPublication . Zegre, Miguel; Barros, J.; Ribeiro, I. A.; Santos, C; Caetano, Liliana Aranha; Gonçalves, L.; Monteiro, F. J.; Ferraz, M. P.; Bettencourt, A.New strategies for the treatment of polymicrobial bone infections are required. In this study, the co-delivery of two antimicrobials by poly(D,L-lactic acid) (PDLLA) scaffolds was investigated in a polymicrobial biofilm model. PDLLA scaffolds were prepared by solvent casting/particulate leaching methodology, incorporating minocycline and voriconazole as clinically relevant antimicrobial agents. The scaffolds presented a sponge-like appearance, suitable to support cell proliferation and drug release. Single- and dual-species biofilm models of Staphylococcus aureus and Candida albicans were developed and characterized. S. aureus presented a higher ability to form single-species biofilms, compared to C. Albicans. Minocycline and voriconazole-loaded PDLLA scaffolds showed activity against S. aureus and C. Albicans single- and dual-biofilms. Ultimately, the cytocompatibility/functional activity of PDLLA scaffolds observed in human MG-63 osteosarcoma cells unveil their potential as a next-generation co-delivery system for antimicrobial therapy in bone infections.
- Release kinetic model and antimicrobial activity of an innovative minocycline and voriconazole co-delivery systemPublication . Zegre, Miguel; Henriques, M.; Ribeiro, I. A.; Caetano, Liliana Aranha; Gonçalves, Lídia M.; Bettencourt, Ana F.Purpose and Strategy: Development of a new local drug-delivery system aiming at bone infection and the modulation of the polymicrobial activity; simultaneous delivery of minocycline and voriconazole, antibacterial and antifungal agents, respectively; polylactide (PDLLA) scaffolds functionalized with collagen and bioglass, osteogenic enhancers.