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Author López Moya, Mario |
Abstract Over the last decades a great deal of expectations have been generated on translation of RNA technology into clinical practice. Although an initial fast translation was foreseen some decades ago, complexities related to administration and delivery have limited introduction as an available therapeutic option. When compared to traditional drugs, RNA technologies require vectors to allow distribution, internalization and ultimately alteration of expression. Mainly, viral and non-viral vectors have been proposed as viable strategies to enhance efficiency. However, use of synthetic vectors have advantages such as versatility, scale-up capabilities and reproducibility. Among the best polymeric vector families are pBAE, a family of biodegrade polymers specifically developed to be non-toxic, form stable nanoparticles and facilitate endosomal scape. Although RNAs hold a great therapeutic potential, treatment of complex multistage diseases usually require a multifactor approach to improve clinical outcomes. Nitric oxide plays a deep effect on epithelial biology and development of dual therapies may hold a strong potential to improve outcomes of complex diseases. Introduction of nitric oxide to pBAE has been accomplished both by adding organic nitrates and thionitrites. Organic nitrate containing pBAE nanoparticles have been found to form stable and effective nanoparticles while showing vasodilation effects in vivo. On the other hand, use of thionitrites as NO releasing moieties, shows a stronger nitric oxide release pattern, self-crosslinking and limited toxicity. Its applications have been directed towards local antimicrobial applications. One of the studied applications has been the coating of airway stents, showing a promising decrease of bacterial colonization. Similar results have been obtained in dermal applications were antimicrobial and dermal vasodilation effects have been observed in preclinical models and early stage clinical trials. In conclusion, this thesis demonstrates that local treatments combined with a new family of pBAE based polymers with integrated capabilities to deliver nitric oxide could be a potential useful tool to treat cardiovascular and epidermal diseases. An additional family of polymers containing nitric oxide, has successfully dedicated to antimicrobial applications. |
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Director Ramos Pérez, Víctor |
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Departament IQS SE - Bioenginyeria |
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Date of defense 2021-01-15
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