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- Chitosan nanoparticles for daptomycin delivery in ocular treatment of bacterial endophthalmitisPublication . Silva, Nádia C.; Silva, Sara; Sarmento, Bruno; Pintado, ManuelaContext: Chitosan nanoparticles were prepared to encapsulate daptomycin and proposed as a delivery system of this antibiotic to the eye for the treatment of bacterial endophthalmitis. Objective: The aim of this study was to develop daptomycin-loaded nanoparticles to apply directly to the eye, as a possible non-invasive and less painful alternative for the treatment of endophthalmitis, increasing the effectiveness of treatment and reducing toxicity associated with systemic administration.Materials and methods: Nanoparticles were obtained by ionotropic gelation between chitosan and sodium tripolyphosphate (TPP). Physicochemical and morphological characteristics of nanoparticles were evaluated, as well as determination of antimicrobial efficiency of encapsulated daptomycin and stability of the nanoparticles in the presence of lysozyme and mucin.Results: Loaded nanoparticles presented mean particle sizes around 200 nm, low polydispersity index, and positive zeta potential. Morphological examination by scanning electron microscopy (SEM) confirmed their small size and round-shaped structure. Encapsulation efficiency ranged from 80 to 97%. Total in vitro release of daptomycin was obtained within 4 h. Determination of minimum inhibitory concentrations (MICs) showed that bacteria were still susceptible to daptomycin encapsulated into the nanoparticles. Incubation with lysozyme did not significantly affect the integrity of the nanoparticles, although mucin positively affected their mucoadhesive properties. Discussion and conclusion: The obtained nanoparticles have suitable characteristics for ocular applications, arising as a promising solution for the topical administration of daptomycin to the eye.
- The importance of antimicrobial peptides and their potential for therapeutic use in ophthalmologyPublication . Silva, Nádia C.; Sarmento, Bruno; Pintado, ManuelaThe reduced effectiveness of some of the most important antibiotics owing to increasing resistance of microorganisms as well as the absence of new classes of antimicrobial agents have been concerning researchers and clinicians in recent years. Thus, the development and approval of new compounds for clinical applications is of great importance. Among these compounds, antimicrobial peptides (AMPs) appear to be excellent candidates for the development of novel antimicrobial agents. Some AMPs and antimicrobial proteins have been shown to be active against relevant pathogens in ocular infections as well as in biofilm eradication from contact lenses. Thus, they are considered promising in the prevention and management of ocular diseases. This review summarises the main classes and characteristics of AMPs and antimicrobial proteins, in particular those found in ocular structures and fluids. Some AMPs with activity against ocular pathogens and their potential as therapeutic agents to treat and prevent ocular infections are emphasised.
- Delivery systems for antimicrobial peptides and proteins: towards optimization of bioavailability and targetingPublication . Costa, Joana R.; Sarmento, Bruno; Silva, Nádia C.; Pintado, ManuelaAntimicrobial peptides (AMPs) and proteins are produced by a wide range of organisms as important elements of their defense mechanisms, forming a large number of antimicrobial compounds that can be used to treat several human infections. The potential for the use of AMPs and antimicrobial proteins in therapeutics is growing, but their application is often limited, due to their poor physical and/or chemical properties. In recent years, several drug delivery systems have been proposed to carry such molecules, in an attempt to overcome the difficulties regarding their properties. However, no review has yet systematized the most relevant information on this subject. Therefore, this review summarizes the work that has been conducted to develop delivery systems for the transport and protection of AMPs and antimicrobial proteins, including their description and potential applications, while highlighting the opportunities for future research in this field.