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Scientific Objectives

Throughout the project we will consider innovative and novel aspects related to the development of capsules and LbL engineered colloids for drug delivery:

1) The use of mesoporous materials with variable pore size as templates: Mesoporous biocompatible microsized particles will be employed as colloidal substrates for LbL assembly profiting from their capability to encapsulate a wide range of molecules of different sizes (anticancer drugs like doxorubicin, antibodies, nucleic acids) and the multiple shapes (spheres, wires). We will develop the means to coat pores of variable size, by LbL, which becomes problematic when the pore size increases above 20 nm due to polyelectrolyte deposition inside the pores as opposed to on top of the pores, thus filling them and preventing the release of encapsulated materials. The LbL strategy will be used as a means to control the release of encapsulated materials and to provide with recognition functions and enhance biocompatibility.

2) Develop the assembly of therapeutic as layers constituents: The delivery of large molecules such as nucleic acids or antibodies encapsulated in the interior of capsules or in the core of colloidal particles is difficult as their release depends on particle degradation or the breaking of the capsule walls. We will explore the fabrication of capsules and LbL coatings based on the therapeutics, as layer constituents, employing polyelectrolytes, lipids, and therapeutics in complexes as a means for their incorporation in the Polyelectrolyte Multilayers (PEMs). We will focus on the encapsulation of silencing RNA (siRNA) and the antibody anti TNF-α.

3) Use of virosomes as a means to endow colloidal particles with biological functions: A strategy for functionalisation by LbL will be combined with biological assembly by means of virosome fusion. This strategy will allow the colloidal particles to be endowed with the fusion capacities of viruses and also to incorporate targeting molecules in a biological environment, where they will retain their biological functionality and will lead to endosomal escape of the drug delivery systems.

4) Biological fate in vitro and in vivo: HYMADE aims to track and understand the fate, translocation and localisation of the capsules and colloids in cells and in animal models, as well as their capacity to carry out their delivery function. This task will require a complex work of labelling. In vitro, a battery of imaging techniques will be applied such as Raman microscopy, Fluorescence Correlation Spectroscopy, Lifetime imaging, etc. In vivo experiments will be performed with Single Photon Emission Computer Tomography (SPECT), and Positron Emission Tomography (PET).

5) Physico chemical characterisation and Transport: The assembly process by LbL will studied in detail, tackling the challenges of pore coating for the mesoporous particles, the assembly of therapeutics as layer components and combining LbL with biological assembly. The physico chemical properties of the assemblies will be studied in detail combining fluorescence techniques, Atomic Force Microscopy, Impedance, etc. Transport properties through polyelectrolytes, which are fundamental for drug delivery will be a central issue in the characterisation, including modelling.