Browsing by Author "Bettencourt, A."
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- 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.
- Dual-loaded chitosan-based nanoparticles: a novel approach for treating polymicrobial osteomyelitisPublication . Zegre, Miguel; Barros, J.; David, A. B.; Fialho, L.; Ferraz, M. P.; Monteiro, F. J.; Caetano, Liliana Aranha; Gonçalves, L.; Bettencourt, A.Developing innovative approaches to target osteomyelitis caused by polymicrobial infections remains a significant therapeutic challenge. In this study, monodispersed chitosan nanoparticles co-loaded with antibacterial (minocycline) and antifungal (voriconazole) agents were successfully prepared. Minocycline presented higher encapsulation efficiency as compared to voriconazole. Thermostability analysis suggested interactions between the co-loaded drugs within the dual-delivery system, potentially limiting voriconazole release. The dual-loaded chitosan nanoparticles exhibited significant in vitro anti-biofilm activity, achieving up to a 90% reduction in polymicrobial biofilms of S. aureus and C. albicans. Additionally, the nanoparticles showed cytocompatibility with a human osteoblast cell line. These findings highlight the potential of this dual-delivery chitosan-based nanoparticle system to address a critical gap in osteomyelitis treatment by targeting both bacterial and fungal pathogens.
- 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 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.
- Research progress on biodegradable polymeric platforms for targeting antibiotics to the bonePublication . Zegre, Miguel; Poljańska, E.; Caetano, Liliana Aranha; Gonçalves, L.; Bettencourt, A.The treatment of bone infections still involves systemic or local antibiotic therapy in high doses for prolonged periods. Current research focuses on the application of different drug delivery systems to the bone, aiming at a targeted local administration that will decrease the number of drugs used and their toxicity, compared to the systemic route. The gold standard in clinical practice is currently poly(methyl methacrylate) (PMMA) cement. The main drawback of PMMA, however, is that it is non-biodegradable, requiring a second follow-up surgery to remove the implant. Biodegradable delivery systems, on the other hand, are easily resorbable within the organism, and less invasive alternative with better patient compliance. Among biodegradable materials, natural and synthetic polymers are being studied as local drug delivery systems due to their excellent biocompatibility, sustained effect, and antibiotic release with high penetrability to infected bone and soft tissue. In this review, we focus on biodegradable polymeric platforms, such as micro- and nanoparticles, scaffolds, and hydrogels, as well as multi-delivery systems for targeting antibiotics to the bone. Additionally, we discuss the reported drug release profiles that provide important information about the systems’ functionality.