TY - JOUR
T1 - Nanoparticles of a polyaspartamide-based brush copolymer for modified release of sorafenib: In vitro and in vivo evaluation
AU - Porsio, Barbara
AU - Giammona, Gaetano
AU - Balasus, Daniele
AU - Pitarresi, Giovanna
AU - Emma, Maria Rita
AU - Cervello, Melchiorre
AU - Balasus, Daniele
AU - Emma, Maria Rita
AU - Puleio, Roberto
AU - Azzolina, Antonina
AU - Loria, Guido Ruggero
AU - Puleo, Stefano
AU - Giammona, Gaetano
PY - 2017
Y1 - 2017
N2 - In this paper, we describe the preparation of polymeric nanoparticles (NPs) loaded with sorafenib for the treatment of hepatocellular carcinoma (HCC). A synthetic brush copolymer, named PHEA-BIB-ButMA (PBB), was synthesized by Atom Trasnfer Radical Polymerization (ATRP) starting from the α-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) and poly butyl methacrylate (ButMA). Empty and sorafenib loaded PBB NPs were, then, produced by using a dialysis method and showed spherical morphology, colloidal size, negative ζ potential and the ability to allow a sustained sorafenib release in physiological environment. Sorafenib loaded PBB NPs were tested in vitro on HCC cells in order to evaluate their cytocompatibility and anticancer efficacy if compared to free drug. Furthermore, the enhanced anticancer effect of sorafenib loaded PBB NPs was demonstrated in vivo by using a xenograft model, by first allowing Hep3B cells to grow subcutaneously into nude mice and then administering sorafenib as free drug or incorporated into NPs via intraperitoneal injection. Finally, in vivo biodistribution studies were performed, showing the ability of the produced drug delivery system to accumulate in a significant manner in the solid tumor by passive targeting, thanks to the enhanced permeability and retention effect.
AB - In this paper, we describe the preparation of polymeric nanoparticles (NPs) loaded with sorafenib for the treatment of hepatocellular carcinoma (HCC). A synthetic brush copolymer, named PHEA-BIB-ButMA (PBB), was synthesized by Atom Trasnfer Radical Polymerization (ATRP) starting from the α-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) and poly butyl methacrylate (ButMA). Empty and sorafenib loaded PBB NPs were, then, produced by using a dialysis method and showed spherical morphology, colloidal size, negative ζ potential and the ability to allow a sustained sorafenib release in physiological environment. Sorafenib loaded PBB NPs were tested in vitro on HCC cells in order to evaluate their cytocompatibility and anticancer efficacy if compared to free drug. Furthermore, the enhanced anticancer effect of sorafenib loaded PBB NPs was demonstrated in vivo by using a xenograft model, by first allowing Hep3B cells to grow subcutaneously into nude mice and then administering sorafenib as free drug or incorporated into NPs via intraperitoneal injection. Finally, in vivo biodistribution studies were performed, showing the ability of the produced drug delivery system to accumulate in a significant manner in the solid tumor by passive targeting, thanks to the enhanced permeability and retention effect.
KW - ATRP; Hepatocellular carcinoma; Sorafenib; Tumor targeting; α-Poly(N-2-hydroxyethyl)-D
KW - L-aspartamide; 3003
KW - ATRP; Hepatocellular carcinoma; Sorafenib; Tumor targeting; α-Poly(N-2-hydroxyethyl)-D
KW - L-aspartamide; 3003
UR - http://hdl.handle.net/10447/247291
UR - http://www.elsevier.com/locate/jconrel
M3 - Article
VL - 266
SP - 47
EP - 56
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -