Nanoparticles of a polyaspartamide-based brush copolymer for modified release of sorafenib: In vitro and in vivo evaluation.

6533b85cfe1ef96bd12bc0a5

RESEARCH PRODUCT

Nanoparticles of a polyaspartamide-based brush copolymer for modified release of sorafenib: In vitro and in vivo evaluation.

Giovanna Pitarresi Guido Ruggero Loria Antonina Azzolina Stefano Puleo Maria Rita Emma Gaetano Giammona Roberto Puleio Antonella Bavuso Volpe Melchiorre Cervello Barbara Porsio Daniele Balasus

subject

3003 Male Hepatocellular carcinoma medicine.medical_treatment Pharmaceutical Science 02 engineering and technology ATRP Pharmacology 01 natural sciences Drug Delivery Systems Copolymer Chemistry ATRP; Hepatocellular carcinoma; Sorafenib; Tumor targeting; Î±-Poly(N-2-hydroxyethyl)-D L-aspartamide; 3003 Liver Neoplasms Sorafenib 021001 nanoscience & nanotechnology Drug delivery 0210 nano-technology medicine.drug Sorafenib Niacinamide Carcinoma Hepatocellular Cell Survival Radical polymerization Intraperitoneal injection L-aspartamide Mice Nude Antineoplastic Agents Enhanced permeability and retention effect 010402 general chemistry Polymethacrylic Acids In vivo Cell Line Tumor medicine Animals Humans neoplasms Protein Kinase Inhibitors Phenylurea Compounds technology industry and agriculture digestive system diseases In vitro 0104 chemical sciences Drug Liberation Tumor targeting Delayed-Action Preparations Biophysics Î±-Poly(N-2-hydroxyethyl)-D Nanoparticles Î±-Poly(N-2-hydroxyethyl)-D L-aspartamide Peptides

description

Abstract 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.

year	journal	country	edition	language
2017-01-01	Journal of controlled release : official journal of the Controlled Release Society

10.1016/j.jconrel.2017.09.014 https://pubmed.ncbi.nlm.nih.gov/28917533