Structural Biology of Alzheimer's Disease
Universitat Autònoma de Barcelona (UAB)
Áreas Temáticas
Código NABS: 120121 - I+D relativa a las Ciencias Naturales financiada con FGU
Área temática principal Biomedicina
Herramientas diagnósticas, pronósticas y terapéuticas
Biociencias y biotecnología
​
Prinicpal Investigators: Josep Cladera and Ramon Barnadas
Gorup Members: Núria Benseny and Mercedes Camacho
​
​
Título:
Nanosistemas lipídidicos para aplicaciones biomédicas.
Title:
Lipid-based nanosystems for biomedical applications.
​
Summary:
Nano-structures based on the self-assembly capacity of lipids with appropriate biocompatibility and biodegradability can be obtained in thelaboratory as vesicles (liposomes, metallosomes) for drug delivery purposes in a variety of different medical conditions. The two PIs of thisproposal have for many years used lipid-based systems as model membranes to study membrane fusion, vesicle aggregation, proteinreconstitution, high scale production of liposomes or lipid droplets in tumor cells. In the last few years they have used liposomes a delivery systems for antiamyloidogenic dendrimers into the brain of an Alzheimers transgenic mice model and the release of carbon monoxide as
an anti-inflammatory gasotransmitter mediated by metallosurfactants in the form of metallosomes. The aim of the present proposal is the design, synthesis and assembly of lipid-based nanosystems for their application in biomedicine with two main objectives: (1) the optimization of a brain delivery system of Alzheimers antiamyloidogenic His-Mal-dendrimers encapsulated in liposomes and the design and assembly of an alternative system consisting of liposomes decorated with histidines via intranasal administration in the mice model; (2) the design and assembly of iron-based CO releasing supramolecular aggregates intended for vascular and inflammatory bowel diseases. The dendrimer-liposome system has already been characterized in our laboratory and we now propose the optimization of the study of its delivery using an Alzheimers mice model for which we already have some preliminary results. As for the design of an alternative approach using liposomes decorated with histidines, it will be addressed from scratch: design, synthesis of the histidine-lipid, assembly, biophysical characterization, cell culture assays (biocompatibility and antiamyloidogenic capacity) and intranasal delivery using the transgenic mice model. In all cases the effects of the lipid-based nanosystems will be assessed via cognitive tests and by the analysis of the brain samples using synchrotron-based imaging techniques that permit measuring amyloid aggregation (formation of both early and fibrillary aggregates) and other related factors such as lipid oxidation and metal cation distribution. The assembly of iron-based CO releasing nanosystems will be carried out via the preparation of liposomes with cyclopentadienyl iron dicarbonyl iodide (CpI); the synthesis of cysteine-CpI
metallosurfactant (CpI-MTS) and the preparation of metallosomes with CpI-MTS; the Biophysical characterization and stability of the CpInanosystems (CpI-liposomes and metallosomes); the evaluation of the CO releasing properties of the CpI nanosystems; biocompatibility assays of the of CpI nanosystems in cell cultures using endothelial, VSMC and Caco-2 cells; the characterization of the effect of CO release and iron absorption and transport of the CpI nanosystems on endothelial and Caco-2 cells; and the study of the metal distribution in cells treated with CPI nanosystems using synchrotron-based imaging techniques. The project is expected to produce results that will enhance the knowledge in the lipid-based for drug delivery with the potential to create new tools with potential therapeutic use in the field of neurodegenerative diseases (delivery of antiamyloidogenic agents in the brain), cardiovascular and gastrointestinal diseases (by localCO delivery using metallosomes).
​
​