Behenic acid solid lipid nanoparticles, prepared according to the coacervation method, were loaded with didodecylmethotrexate, an esther prodrug of methotrexate, which was previously tested in vitro for cytotoxicity against glioblastoma human primary cultures. Nanoparticles conjugation with an ApoE mimicking chimera peptide was performed, in order to obtain active targeting to the brain. Biodistribution studies in healthy rats assessed the superiority of ApoE conjugated formulation, which was employed in efficacy studies on a F98/Fischer glioma model. Differences were observed in tumor growth rate (measured through MRI), as well as in apoptosis between control and treated rats, even if not significant. In vitro tests on F98 cultured cells assessed their susceptibility to treatment, with consequent apoptosis, and allowed us to hypothesize a direct correlation between the in vivo administered formulation and the observed apoptosis.

Solid lipid nanoparticles by coacervation loaded with a methotrexate prodrug: preliminary study for glioma treatment

BATTAGLIA, Luigi Sebastiano
First
;
MUNTONI, Elisabetta;CHIRIO, Daniela;PEIRA, Elena;annovazzi, laura;SCHIFFER, Davide;RIGANTI, Chiara;SALAROGLIO, IRIS CHIARA;LANOTTE, Michele Maria Rosario;PANCIANI, PIER PAOLO;CAPUCCHIO, Maria Teresa;VALAZZA, Alberto;BIASIBETTI, ELENA;GALLARATE, Marina
Last
2017-01-01

Abstract

Behenic acid solid lipid nanoparticles, prepared according to the coacervation method, were loaded with didodecylmethotrexate, an esther prodrug of methotrexate, which was previously tested in vitro for cytotoxicity against glioblastoma human primary cultures. Nanoparticles conjugation with an ApoE mimicking chimera peptide was performed, in order to obtain active targeting to the brain. Biodistribution studies in healthy rats assessed the superiority of ApoE conjugated formulation, which was employed in efficacy studies on a F98/Fischer glioma model. Differences were observed in tumor growth rate (measured through MRI), as well as in apoptosis between control and treated rats, even if not significant. In vitro tests on F98 cultured cells assessed their susceptibility to treatment, with consequent apoptosis, and allowed us to hypothesize a direct correlation between the in vivo administered formulation and the observed apoptosis.
2017
12
639
656
Solid lipid nanoparticles; didodecylmethotrexate, apoE, blood-brain barrier; glioblastoma
Battaglia, L; Muntoni, E; Chirio, D; Peira, E; Annovazzi, L; Schiffer, D; Mellai, M; Riganti, C; Salaroglio, Ic; Lanotte, M; Panciani, P; Capucchio, M...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1627489
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