De Capua, Alberta (2020) Multi-functional emulsion based nanocapsules for active targeting. [Tesi di dottorato]
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Testo
DeCapua_Alberta_32.pdf Download (5MB) | Anteprima |
| Tipologia del documento: | Tesi di dottorato | ||||||
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| Lingua: | English | ||||||
| Titolo: | Multi-functional emulsion based nanocapsules for active targeting | ||||||
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| Data: | 2020 | ||||||
| Istituzione: | Università degli Studi di Napoli Federico II | ||||||
| Dipartimento: | Ingegneria Chimica, dei Materiali e della Produzione Industriale | ||||||
| Dottorato: | Ingegneria dei prodotti e dei processi industriali | ||||||
| Ciclo di dottorato: | 32 | ||||||
| Coordinatore del Corso di dottorato: |
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| Data: | 2020 | ||||||
| Parole chiave: | nanoemulsions; active targeting; drug delivery; peptides. | ||||||
| Settori scientifico-disciplinari del MIUR: | Area 03 - Scienze chimiche > CHIM/09 - Farmaceutico tecnologico applicativo Area 09 - Ingegneria industriale e dell'informazione > ING-IND/22 - Scienza e tecnologia dei materiali Area 09 - Ingegneria industriale e dell'informazione > ING-IND/34 - Bioingegneria industriale |
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| Depositato il: | 22 Mar 2020 23:53 | ||||||
| Ultima modifica: | 31 Mar 2022 01:00 | ||||||
| URI: | http://www.fedoa.unina.it/id/eprint/13161 |
Abstract
Multi-functional oil in water nanoemulsions (O/W NEs) are an ideal carrier for drug delivery thanks to their ability to dissolve hydrophobic drugs and natural substances like curcumin and coenzyme Q10 (CoQ10), and protect their cargo from hydrolysis and enzymatic degradation under physiological conditions. The stabilization of O/W NEs by means of a natural polymer coating, obtained through the layer by layer (LbL) methodology, is extremely important to obtain a product stable enough to build up dimensionally controllable multilayer nanocapsules of interest for nanomedicine. The improvement of therapeutic formulation efficacy is correlated to its ability to selectively target, with specific moieties, diseased tissue without affecting healthy sites. In this perspective, the first part of my PhD project concerns the development of an innovative tool based on an O/W core-LbL bilayer shell made of completely biodegradable materials. It was functionalized with biotin moieties on the external layer constituted by hyaluronic acid (HA), in order to exploit streptavidin-biotin affinity, and therefore expose any kind of ligands outside the nanocapsules. A complete thermodynamic characterization of streptavidin interaction with biotinylated tool was performed by isothermal titration calorimetric (ITC) analysis. The second part of the PhD project will focus on the use of such O/W NEs coated with peptides meant for active targeting via the biotin-streptavidin strategy. In other words, it consists in the attachment of peptides to the outer surface of O/W NEs that become able to specifically bind to target receptors present on cell surface. Two receptors have been considered: CD44, highly over-expressed in many cancer cells; and transferrin receptor (TfR) over-expressed on the blood brain barrier (BBB). In both cases, two peptide sequences, able to recognize them, were identified. Thanks to high binding affinity with biotin, streptavidin was used as linker to conjugate the synthetized peptide to the entire systems, using a decoration strategy, while keeping nano-carrier stability. Biological tests demonstrated that peptide functionalized O/W NEs are able to accumulate and internalize in specific cells, when specific peptides are exposed, thanks to ligand-receptor binding. Finally, it was investigated the use of O/W NEs to prevent or support oncological patients during the clinical treatment. In this scenario, it was demonstrated the cardioprotective and hepatoprotective effects of Coenzyme Q10 loaded O/W NEs against Doxorubicin and Trastuzumab toxicities. O/W NEs showed high stability and loading ability, increases cell viability both in hepatocytes and cardiomyocytes during anticancer treatments. The future upgrade in this case will be to use the above mentioned coating strategy with peptides able to selectively target liver and cardiovascular tissues.
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