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Development and characterization of biomimetics nanoparticles encapsulating ponatinib, a multi-targeted tyrosine-kinase inhibitor, for the treatment of the Osteosarcoma, a type of bone cancer

Gherardo Baudo

Development and characterization of biomimetics nanoparticles encapsulating ponatinib, a multi-targeted tyrosine-kinase inhibitor, for the treatment of the Osteosarcoma, a type of bone cancer.

Rel. Danilo Demarchi. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2020

Abstract:

Osteosarcoma is the most frequent primary cancer that affects bone. Current treatments have severe limitations and side effects in young population so new therapies are needed. Recently ponatinib gave good results in the treatment of osteosarcoma in clinical trials, however it showed to increase incidence of arterial thrombotic events and cardiovascular toxicities. Therefore, it was hypothesized that by encapsulating the ponatinib inside a nanoparticle formulation will reduce the pharmacokinetic profile and the detrimental side effects. The aim of this work was to design, develop and characterize new biomimetic nanoparticles (leukosomes) able to encapsulate ponatinib, a new therapeutic agent to treat osteosarcoma. Bovine serum albumin (BSA) was used as carrier for increasing the ponatinib solubility and different BSA concentrations (2mg/mL, 20mg/mL and 200mg/mL) and ponatinib:BSA (1:2, 1:20, 1:100, 1:200) were tested to find the highest encapsulation efficiency. The nanoparticles were characterized in terms of size (~150nm), polydispersity index (~0.15 a.u.), zeta potential (~-2.5mV), nanoparticles concentration (~4.15E+12 particles/mL) and encapsulation efficiency (~5%). Moreover, the fabrication protocol was demonstrated reproducible and stable (N > 9). The potential of this platform to be used on 577 osteosarcoma cell line as a future targeted osteosarcoma treatment was tested by in vitro studies. According to the preliminary results it’s was seen that ponatinib encapsulating in leukosomes were efficiently internalized in 577 cells at 24 hours and reduced the half maximal inhibitory concentration (IC50) from 3μM to 0.9μM. We aspect that this platform could significantly decrease ponatinib side effects in vivo.

Relatori: Danilo Demarchi
Anno accademico: 2019/20
Tipo di pubblicazione: Elettronica
Numero di pagine: 147
Informazioni aggiuntive: Tesi secretata. Fulltext non presente
Soggetti:
Corso di laurea: Corso di laurea magistrale in Ingegneria Biomedica
Classe di laurea: Nuovo ordinamento > Laurea magistrale > LM-21 - INGEGNERIA BIOMEDICA
Aziende collaboratrici: NON SPECIFICATO
URI: http://webthesis.biblio.polito.it/id/eprint/13743
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