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Author Hernández Lobato, Noelia |
Abstract Glioblastoma multiforme (GBM) is the most frequent brain tumour and it is characterized for having a high mortality rate, being highly invasive and progressing very rapidly. As a result, the life expectancy of patients after diagnosis is between 15 and 20 months. Currently, glioblastoma is an incurable disease. Available treatments are inefficient because of the presence of the blood brain barrier, which hampers the arrival of therapeutics to the brain, as well as the presence of glioblastoma stem cells, that are able to regenerate the tumour after surgical resection. Here we propose the use of poly(ß-amino ester)s (pBAE) nanoparticles to carry a targeted gene therapy to the brain. To enable this selective delivery, several polymeric coatings (hyaluronic acid (HA), poly(L-glutamic acid) (PGA) and poly(HPMA-co-MAC) are tested with the aim to reduce the nanoparticles transfection efficiency in undesired tissues. Hyaluronic acid and poly(L-glutamic acid) are two anionic polymers that are already present in nature and they are characterized for being biodegradable and biocompatible. In the case of poly(HPMA-co-MAC), it is synthesized de novo from N-(2-hydroxy)propyl methacylamide (HPMA) and N-methacryloyl-6-aminohexanoic acid (MAC) monomers. HPMA is used because of its low immunogenicity and low blood clearance rate, whereas, MAC is used for linkage of the coating to the core polymer with a pH-sensitive bond or functionalization with targeting ligands. In this work, we have demonstrated that PGA can be used to coat OM-pBAE nanoparticles and modulate their surface charge. Moreover, poly(HPMA-co-MAC) was synthesized de novo and preliminary studies were carried out in its functionalization for making it selective to the pH in the tumour microenvironment. |
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Director Oller Salvia, Benjamí |
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Degree IQS SM - Master’s Degree in Pharmaceutical Chemistry |
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Date 2020-06-23
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