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Novel Quatsome nanovesicles, prepared using CO2, for the development of advanced nanomedicines

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Universitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació

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[eng] Quatsomes are lipid-based nanovesicles developed by Nanomol group, composed of ionic surfactants and sterol derivatives. Regarding their properties, Quatsomes have shown to be highly homogenous and stable for years, important requirements for their use in pharmaceutical products. In recent years, the application of Quatsomes for drug delivery and bioimaging has been explored. In this work, new Quatsome formulations have been developed, to facilitate their use as intravenous drug delivery systems and increase their potential as bioimaging probes. In order to design these new Quatsomes for intravenous administration, the cholesterol and the positive MKC surfactant (myristalkonium chloride) were selected, which are molecules used in many parenteral formulations on the EU and USA market. The MKC- Quatsomes have homogenous particle size distributions, with diameters around 85 nm. The stability of these MKC-Quatsomes is dependent on the chloride ions in the medium, being stable at physiological conditions. These MKC-Quatsomes were prepared in different media that are suitable for parenteral administration using the DELOS-SUSP methodology. Moreover, these MKC-Quatsomes are stable without changing their physicochemical properties in storage conditions, dilution and human serum. Furthermore, the MKC-Quatsomes were intravenously administered in mice, where the biodistribution assays showed nanovesicle accumulation in tumors, liver, spleen, and kidneys. No histological alteration or toxicity was observed in any of these organs. To enhance the functionality of Quatsomes as bioimaging probes Quatsomes have been labeled with FRET-pair dyes (the indocarbocyanine DiI and DiD), which allows to reduce the self-absorption by the animal’s tissues. We confirmed that this strategy yields bioprobes of high brightness, photostability, and FRET efficiency. Moreover, when the dyes are placed in the Quatsome’s membranes, there is no change in the cytotoxicity. Finally, in order to acquire new functionalities, Quatsomes have been tuned. Their membrane components have been modified or changed, improving or gaining new functionalities. In this sense, PEG molecules have been anchored to the Quatsomes’ membrane and the negative SDS molecule has been used as ionic surfactant in the Quatsomes, achieving new negative Quatsomes. In summary, the results achieved in this thesis support the application of Quatsomes as new nanomedicines for intravenous drug delivery and bioimaging probes.

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Tesis Doctorals - Facultat - Farmàcia i Ciències de l'Alimentació

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Novel Quatsome nanovesicles, prepared using CO2, for the development of advanced nanomedicines