Biblioteca
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The Library of FMV supports students, researchers and teachers of FMV and external users in the provision and search of books, periodicals and articles necessary for their studies. It has around 42.800 books and 1.670 periodicals, among other materials like microfilms and CD/ROMs.
The users of the library should have the institution card and have free access to all items present in the public area.
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Browsing Biblioteca by advisor "Aguiar, Sandra Isabel Rodrigues de"
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- Antibiotic-lipid based nanosystem as a tool to specifically target Staphylococcus aureus biofilmsPublication . Ferreira, M.C. Magda Sofia Catroga Ferreira; Aguiar, Sandra Isabel Rodrigues de; Gaspar, Maria Manuela de Jesus Guilherme; Bettencourt, Ana Francisca de Campos SimãoAbstract - Hospital acquired infections (HAIs) is one of the leading causes of death worldwide, with Staphylococcus aureus being among the most prevalent microorganisms implicated in these infections. The ability of S. aureus to form biofilms and evade the immune system, along with the emergence of multidrug-resistant strains (MDR), exacerbates the complexity of eradicating infections. Conventional therapies characterized by prolonged antibiotic regiments have a poor rate of success, mainly due to the reduced penetration of antibiotics through the biofilms and low accumulation levels at infected sites. The ineffectiveness of current treatments has stimulated extensive research into the development of innovative therapeutic approaches. To address this need, the aim of this thesis was the development of a nanosystem by incorporating an antibiotic into liposomes, taking advantage of the unique benefits offered by these nanotechnological platforms. For this purpose, we first explored the antibacterial activity of three common antibiotics in clinical use – levofloxacin (LEV), vancomycin (VCM) and rifabutin (RFB) – against a reference strain of S. aureus (ATCC®25923™) in both planktonic and biofilm states. Subsequently, the antibiotics were incorporated into liposomes with different lipid compositions, and their incorporations parameters were assessed. Free RFB displayed the most potent antibacterial effect with MIC and MBIC50 below 0.006 µg/mL, along with the highest antibiotic loading capacity when nanoformulated, preserving its antibacterial activity. Based on these results, RFB was selected for further in vitro studies and the influence of the different lipid compositions on bacterial biofilm interactions was assessed, using a biofilm transwell model and confocal scanning laser microscopy analysis. It was observed that the positively charged RFB liposomes (LIP3) exhibited the highest interaction with biofilms. Nevertheless, RFB incorporated in negatively charged liposomes with fusogenic properties (LIP1) displayed lower MBIC50 values. Preliminary safety assessment of RFB formulations towards osteoblast and fibroblast cell lines indicated that a reduction in cell viability was only observed for the LIP3. Taking this into account, LIP1 was selected to move forward. Following these findings, the potential of free RFB was validated in a collection of S. aureus clinical isolates to provide a more accurate reflection of the challenges faced in real-world settings, in both planktonic (n=114) and biofilm (n=40) states. Additionally, the antibacterial activity of RFB incorporated in our developed liposome (LIP1) was validated against a set of clinical isolates (n=40) in both states. In conclusion, all the work developed contributed to the pursuit of effective therapeutic strategies for planktonic and biofilm-associated S. aureus infections, by exploring the potential of antibiotic repurposing and incorporating them into liposomes
- Atividade antimicrobiana in vitro da ceftriaxona encapsulada em lipossomas contra estirpes clínicas isoladas de animais de companhia com diagnóstico de infeção do trato urinárioPublication . Diogo, Rita Alexandra Correia; Aguiar, Sandra Isabel Rodrigues de; Neves, Solange Judite Roque Coelho Alves GilAs infeções do trato urinário ocorrem de forma frequente, na prática clínica veterinária, sendo responsáveis pela utilização de antibióticos no seu tratamento. O recurso excessivo a estes fármacos, tanto na medicina veterinária como na medicina humana, tem levado ao desenvolvimento e aumento das resistências antimicrobianas. Como consequência, ocorreu uma diminuição dos antibióticos disponíveis e eficazes para o tratamento de infeções bacterianas, transformando-se numa problemática a nível global. Perante esta situação, têm sido desenvolvidas novas abordagens ao tratamento de infeções bacterianas, que se têm vindo a demonstrar eficazes e promissoras, sendo uma delas o encapsulamento de antibióticos em lipossomas. No presente estudo, foi avaliada e comparada a atividade antimicrobiana, in vitro, da ceftriaxona livre e encapsulada em lipossomas, contra 13 estirpes clínicas de animais de companhia hospitalizados na Unidade de Isolamento e Controlo Biológico com diagnóstico confirmado de infeção do trato urinário. A ceftriaxona foi encapsulada em lipossomas com propriedades fusogénicas e uma composição lipídica PC:DOPE:CHEMS (rácio molar 4:4:2), com uma eficácia de encapsulação de 6%. A atividade antimicrobiana, da ceftriaxona lipossomal e livre, foi avaliada através da determinação da concentração mínima inibitória, pelo método de microdiluição em placa. Os resultados obtidos demonstraram que o efeito antimicrobiano da ceftriaxona encapsulada foi inferior ao da ceftriaxona livre, tanto para as estirpes classificadas como suscetíveis como para as MDR. Embora a formulação lipossomal utilizada neste estudo tenha características fusogénicas, o que lhe permite uma melhor interação com as bactérias, a eficácia de encapsulação demonstrou-se baixa, o que pode explicar estes resultados. Em suma, a atividade antimicrobiana, in vitro, da formulação lipossomal não apresentou um desempenho superior, quando comparada com a formulação livre. Contudo, a formulação lipossomal com propriedades fusogénicas demonstrou efeito antibacteriano contra algumas estirpes. Como perspetiva futura, as características fusogénicas da formulação lipossomal devem ser preservadas, para que a interação entre lipossoma e bactéria se mantenha, mas será necessário aumentar a eficácia de encapsulação.
- In vitro antimicrobial activity of liposomal ceftriaxone and liposomal amoxicillin and clavulanic acid against clinical isolates of companion animals with urinary tract infectionsPublication . Ögren, Maria Luísa Sales Baptista; Neves, Solange Judite Roque Coelho Alves Gil; Aguiar, Sandra Isabel Rodrigues deUrinary tract Infections accounts for major use of antimicrobials in veterinary medicine. Nevertheless, its overuse has led to the emergence of antimicrobial resistance and subsequent absence of effective antibiotics. Hence, new therapeutic approaches are required. A promising strategies is the encapsulation of currently available antibiotics in liposomes. The present study was undertaken to evaluate the in vitro antimicrobial activity of free and liposome-encapsulated ceftriaxone and amoxicillin and clavulanic acid, against 14 clinical isolates of companion animals with urinary tract infections. Their antimicrobial activity was measured by means of minimum inhibitory concentration determination, through the broth microdilutions method, whereas the assessment of the bacterial growth was achieved by a colorimetric method. Ceftriaxone and amoxicillin and clavulanic acid were successfully encapsulated in the liposome. However, the minimum inhibitory concentration values of the liposome-encapsulated ceftriaxone were 4 to 16 times higher than those of the corresponding free antibiotic, against the E. coli and K. pneumoniae isolates. This result was probably due to a low liposome-bacterium interaction. The liposome-encapsulated amoxicillin and clavulanic acid didn’t show antibacterial activity and none of the studied liposomal forms exhibited antibacterial activity against the P. aeruginosa isolates owing to its high bacterial resistance. Overall, the liposomal encapsulation of the antibiotics didn’t enhance the in vitro antibacterial activity when compared to the existing drug. Nevertheless, it showed antibacterial potential, suggesting that for further investigation the extent of the interaction with the bacteria should be improved through the variation of the physicochemical properties of the liposome.