Nanocarriers for the oral administration of therapeutic macromolecules

The main goal of this thesis has been the generation of knowledge towards the advancement of the oral administration of peptides. The specific objective has been to study how the composition and surface properties of lipid-based nanocarriers influence i) their capacity to load hydrosoluble peptides...

Descripción completa

Detalles Bibliográficos
Autor: Santalices Ramos, Irene
Tipo de recurso: tesis doctoral
Fecha de publicación:2018
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/18026
Acceso en línea:http://hdl.handle.net/10347/18026
Access Level:acceso abierto
Palabra clave:Materias::Investigación::32 Ciencias médicas::3209 Farmacología::320908 Preparación de medicamentos
Materias::Investigación::32 Ciencias médicas::3209 Farmacología::320903 Evaluación de medicamentos
Descripción
Sumario:The main goal of this thesis has been the generation of knowledge towards the advancement of the oral administration of peptides. The specific objective has been to study how the composition and surface properties of lipid-based nanocarriers influence i) their capacity to load hydrosoluble peptides and ii) their ability to overcome the biological barriers associated to the oral modality of administration. Throughout this study, we developed a novel mixed nanosystem (nanoemulsion co-existing with micelles) able to load hydrophobically-modified insulin with a 100 % association efficiency. In brief, this nanosystem showed a great stability and miscibility in bio-relevant media, acceptable mucodiffusive properties and ability to interact and enter the intestinal cells, without relevant cytotoxic effects. Interestingly, the promising in vitro behavior of this insulin-loaded nanosystem was translated into a moderate hypoglycemic response (≈ 20−30 %) following intestinal administration to rats.