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Hydrogels as vehicles for the topical application of therapeutic bacteriophages
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A resistência aos antibióticos representa atualmente uma crise de saúde global que ameaça comprometer a capacidade de tratar de modo eficaz algumas infeções bacterianas. A utilização excessiva e por vezes desnecessária de antibióticos levou ao aparecimento de agentes patogénicos multirresistentes que não conseguem ser devidamente eliminados com os tratamentos atualmente disponíveis. Devido ao aumento do número de infeções e mortes provocadas por este tipo de microrganismos, a Organização Mundial de Saúde (OMS) divulgou uma lista onde estão identificados os agentes patogénicos mais problemáticos no contexto das resistências, de modo a direcionar a pesquisa e desenvolvimento de novos fármacos antibacterianos. As infeções cutâneas, que são frequentemente encontradas na prática clínica, também testemunharam um aumento de microrganismos resistentes a antibióticos, o que tem dificultado o tratamento de várias infeções da pele comuns, como as que estão associadas a queimaduras ou úlceras do pé diabético.
Devido à ineficácia crescente da antibioterapia, torna-se necessário encontrar terapêuticas alternativas ou complementares aos antibióticos convencionais. Os bacteriófagos (fagos), vírus que infetacm e destroem as células bacterianas, têm demonstrado potencial enquanto terapêutica alternativa.
Apesar de os bacteriófagos poderem ser administrados por diferentes vias, no âmbito deste trabalho estudou-se o desenvolvimento de formulações tópicas que permitam a sua aplicação em diferentes infeções ao nível da pele. Devido ao seu elevado conteúdo em água e biocompatibilidade, os hidrogeles poderão funcionar como veículos ideais para a estabilização, entrega e presença prolongada de fagos no local de infeção. Foram desenvolvidos 3 hidrogeles com diferentes concentrações de polímero, contendo fagos, e foi estudada a sua ação bactericida in vitro contra Staphylococcus aureus e Pseudomonas aeruginosa, dois dos microrganismos críticos presentes na lista da OMS, e que frequentemente estão associados a infeções cutâneas.
Os resultados obtidos permitiram concluir que os hidrogeles têm potencial para serem um bom veículo para os fagos, uma vez que podem providenciar um ambiente estabilizador destes agentes e favorecer a manutenção da sua atividade bactericida. No entanto, verificou-se que a manutenção da viabilidade dos fagos pode ser variável consoante a composição dos hidrogeles e do fago incorporado, tornando-se assim necessário um estudo prévio da combinação hidrogel/fago de modo a obter a maior ação bactericida possível.
Antibiotic resistance currently represents a global health crisis that threatens to compromise the ability to effectively treat some bacterial infections. The excessive and sometimes unnecessary use of antibiotics has led to the emergence of multi-resistant pathogens that cannot be properly eliminated with currently available treatments. Due to the increase in the number of infections and deaths caused by this type of microorganisms, the World Health Organization (WHO) released a list identifying the most problematic pathogens in the context of resistance, to direct research and development of new antibacterial drugs. Skin infections, which are frequently encountered in clinical practice, have also witnessed an increase in antibiotic-resistant microorganisms, which has hampered the treatment of several common skin infections such as burns or diabetic foot ulcers. Due to the increasing ineffectiveness of antibiotic therapy, it is necessary to find alternative or complementary therapies to conventional antibiotics. Bacteriophages (phages), viruses that infect and destroy bacterial cells, have demonstrated potential as an alternative therapy. Although bacteriophages can be administered by different routes, within the scope of this work we studied the development of topical formulations that allow their application in different infections at the skin level. Due to their high-water content and biocompatibility, hydrogels could function as ideal vehicles for the stabilization, delivery and prolonged presence of phages at the site of infection. Three hydrogels were developed with different polymer concentrations, containing phages, and their in vitro bactericidal action was studied against Staphylococcus aureus and Pseudomonas aeruginosa, two of the critical microorganisms present in the WHO list, which are frequently associated with skin infections. The results obtained allowed us to conclude that hydrogels have the potential to be a good vehicle for phages, as they can provide a stabilizing environment for these agents and favour the maintenance of their bactericidal activity. However, it was found that the maintenance of phage viability can be variable depending on the composition of the hydrogels and the incorporated phage, making it necessary to carry out a prior study of the hydrogel/phage combination in order to obtain the greatest possible bactericidal action.
Antibiotic resistance currently represents a global health crisis that threatens to compromise the ability to effectively treat some bacterial infections. The excessive and sometimes unnecessary use of antibiotics has led to the emergence of multi-resistant pathogens that cannot be properly eliminated with currently available treatments. Due to the increase in the number of infections and deaths caused by this type of microorganisms, the World Health Organization (WHO) released a list identifying the most problematic pathogens in the context of resistance, to direct research and development of new antibacterial drugs. Skin infections, which are frequently encountered in clinical practice, have also witnessed an increase in antibiotic-resistant microorganisms, which has hampered the treatment of several common skin infections such as burns or diabetic foot ulcers. Due to the increasing ineffectiveness of antibiotic therapy, it is necessary to find alternative or complementary therapies to conventional antibiotics. Bacteriophages (phages), viruses that infect and destroy bacterial cells, have demonstrated potential as an alternative therapy. Although bacteriophages can be administered by different routes, within the scope of this work we studied the development of topical formulations that allow their application in different infections at the skin level. Due to their high-water content and biocompatibility, hydrogels could function as ideal vehicles for the stabilization, delivery and prolonged presence of phages at the site of infection. Three hydrogels were developed with different polymer concentrations, containing phages, and their in vitro bactericidal action was studied against Staphylococcus aureus and Pseudomonas aeruginosa, two of the critical microorganisms present in the WHO list, which are frequently associated with skin infections. The results obtained allowed us to conclude that hydrogels have the potential to be a good vehicle for phages, as they can provide a stabilizing environment for these agents and favour the maintenance of their bactericidal activity. However, it was found that the maintenance of phage viability can be variable depending on the composition of the hydrogels and the incorporated phage, making it necessary to carry out a prior study of the hydrogel/phage combination in order to obtain the greatest possible bactericidal action.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Bacteriophages Antibiotic resistance Phage therapy Topical formulations Mestrado Integrado - 2023