Lipid nanoparticles for therapeutic proteins delivery

• Autor(a) principal: Seck, Fatumata Ramadana Gomes
• Data de Publicação: 2021
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.1/19486
• topic: Solid lipidic nanoparticle; Nanostructured lipid carrier; Therapeutic protein; Delivery system; Insulin; Encapsulation; Drug delivery; Domínio/Área Científica::Ciências Médicas::Outras Ciências Médicas

Therapeutic proteins are bioactive compounds used for the treatment and prevention of several diseases. These compounds are usually well-tolerated, present a high specific activity, few adverse reactions, and a wide range of applications. Nevertheless, they also present physicochemical instability, with susceptibility to suffer degradation. The use of nanocarrier systems protects the protein structure, improve its bioavailability and enhance its sustained or controlled release. There has been an emerging interest in lipid nanoparticles as carriers for drug delivery. Solid lipid nanoparticles (SLN) are considered the first-generation of lipid nanoparticles, composed of a solid lipid matrix of one or more biocompatible and biodegradable lipids, solid at both room and body temperature. Nanostructured lipid carriers (NLC) are the second generation of lipid nanoparticles, on which the solid lipid matrix is replaced by a blend of liquid and solid lipid. The incorporation of a liquid lipid increases the imperfections in the matrix core which allows an increased encapsulation efficiency and decreased expulsion of the encapsulated drugs during storage. Nevertheless, the application of the NLC for the encapsulation of therapeutic proteins is not well established yet and it urges the need to optimize production methods that do not compromise the protein structure during the encapsulation process. We have optimized the production of an insulin-loaded NLC formulation achieving a particle size of about 200 nm, zeta potential of -18 mV and more importantly, an encapsulation efficiency of about 85% and loading capacity of 11%, which are promising features for different applications. Therefore, the objective of this work was to address the use of lipid nanoparticles for therapeutic proteins delivery. Thus, using insulin as a model protein, it was developed a production method to encapsulate therapeutic proteins into NLC. It is foreseen the opening of a new paradigm in the delivery of therapeutic proteins using NLC.