ELISAMARIA TASCA

PhD

PhD program:: XXXIII


tutor: Luciano Galantini
advisor: Mauro Giustini

Thesis title: Doxorubicin: from main character to guest actor

Self-assembly is a widespread phenomenon spanning from chemistry to biology. In this context, my PhD dissertation focuses on the study of the self-assembly behaviour of the anticancer drug doxorubicin hydrochloride (DX) and of a triblock copolymer of the poloxamers family (precisely F127) that gives rise to polymeric micellar aggregates where DX can be hosted. More than 50% of DX molecules in water solutions, even at 10-5M concentration, are found in the form of dimers. By rising the DX concentration to 10-2 M (where practically all the molecules are in the form of dimers) and by adding a critical amount of NaCl at a well- defined temperature, the solution turns into a thixotropic gel. SAXS data have evidenced the presence of long fibres made of hundreds of DX molecules arranged to form tridimensional helices whose entanglement gives rise to the observed increase in the macroscopic viscosity. The resulting system is characterized by an extremely high supramolecular chirality and by quite peculiar fluorescent properties. One of the main concerns in the clinical use of DX is related to the severe side effects (cardiotoxicity being the principal) that impair its use. One of the most successful strategies to overcome this problem is to host DX into suitable carriers (liposomes, mainly). Above well defined critical micellar concentration and temperature (cmc and cmt, respectively), poloxamers self-assemble into core-shell supramolecular micellar structures that can host hydrophobic species in their inner apolar core. Due to the DX cationic nature, to enhance its solubility in the apolar inner compartment of the micelles, the driving effect of the anionic bile salt sodium cholate (NaC) has been exploited. The resulting systems were characterized by scattering and fluorescence techniques taking advantage of the intrinsic fluorescence of DX. Indeed, in the presence of NaC, DX penetrates the apolar core region of F127/NaC mixed micelles, as evidenced both by the change in the fluorescence and UV-Vis spectra and by the increase in its fluorescence lifetime. The hydrophobic core of NaC/F127 polymeric micelles provides a safe environment for DX, slowing down its degradation and, as demonstrated by the biological results (MTT assays and confocal images), increasing its latency time once in the tumours cells. These features result into a time-dependent release of DX leading to an attenuation of the undesired side-effects.

Research products

  • 11573/1107935 - 2018 - A stereochemically driven supramolecular polymerization (01a Articolo in rivista)
    TASCA, ELISAMARIA; D'ABRAMO, MARCO; GALANTINI, LUCIANO; PAVEL, NICOLAE VIOREL; GIUSTINI, MAURO
  • 11573/1123419 - 2018 - F127 pluronic in coformulation with sodium cholate as hosting system for doxorubicin (04f Poster)
    TASCA, ELISAMARIA; GIUSTINI, MAURO; GALANTINI, LUCIANO
  • 11573/1123422 - 2017 - Self-assembly of doxorubicin into gels (04f Poster)
    TASCA, ELISAMARIA; GIUSTINI, MAURO; D'ABRAMO, MARCO; GALANTINI, LUCIANO
  • 11573/1216535 - 2019 - A fluorescence study of the loading and time stability of doxorubicin in sodium cholate/PEO-PPO-PEO triblock copolymer mixed micelles (01a Articolo in rivista)
    TASCA, ELISAMARIA; DEL GIUDICE, ALESSANDRA; GALANTINI, LUCIANO; GIUSTINI, MAURO
  • 11573/1292243 - 2019 - Sodium cholate/PEO-PPO-PEO triblock copolymer mixed micelles as stealth nanocarrier for doxorubicin (04d Abstract in atti di convegno)
    TASCA, ELISAMARIA; DEL GIUDICE, ALESSANDRA; GALANTINI, LUCIANO; GIUSTINI, MAURO
  • 11573/1292229 - 2018 - Doxorubicin and self-assembly: from main character to guest actor (04f Poster)
    TASCA, ELISAMARIA; GIUSTINI, MAURO; GALANTINI, LUCIANO
  • 11573/1336181 - 2019 - Antibacterial layer-by-layer films of poly(acrylic acid)-gentamicin complexes with a combined burst and sustainable release of Gentamicin (01a Articolo in rivista)
    ANDREOZZI, PATRIZIA; TASCA, ELISAMARIA
  • 11573/1427354 - 2020 - Poloxamer/sodium cholate co-formulation for micellar encapsulation of doxorubicin with high efficiency for intracellular delivery. An in-vitro bioavailability study (01a Articolo in rivista)
    TASCA, ELISAMARIA; DEL GIUDICE, ALESSANDRA; GALANTINI, LUCIANO; SCHILLEN, KARIN MARIA; GIUSTINI, MAURO
  • 11573/1277998 - 2019 - The self-association equilibria of doxorubicin at high concentration and ionic strength characterized by fluorescence spectroscopy and molecular dynamics simulations (01a Articolo in rivista)
    TASCA, ELISAMARIA; ALBA, JOSEPHINE; GALANTINI, LUCIANO; D'ABRAMO, MARCO; GIUSTINI, MAURO
  • 11573/1571300 - 2021 - Polarity studies of single polyelectrolyte layers in polyelectrolyte multilayers probed by steady state and life time doxorubicin fluorescence (01a Articolo in rivista)
    TASCA, ELISAMARIA; GIUSTINI, MAURO; MOYA, SERGIO ENRIQUE

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