title: Galactosylated polymeric carriers for liver targeting of sorafenib.
abstract: In this paper, we describe the preparation of liver-targeted polymeric micelles potentially able to carry sorafenib to hepatocytes for treatment of hepatocarcinoma (HCC), exploiting the presence of carbohydrate receptors, ASGPR. These micelles were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-d,l-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, leading to PHEA-EDA-PLA-GAL copolymer. Liver-targeted sorafenib-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometer size and slightly positive zeta potential. Biodistribution studies on mice demonstrated, after oral administration of sorafenib loaded PHEA-EDA-PLA-GAL micelles, the preferential sorafenib accumulation into the liver. This finding raises hope in terms of future drug delivery strategy of sorafenib-loaded micelles targeted to the liver for the HCC treatment.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sezione di Chimica e Tecnologie Farmaceutiche, Università di Palermo, via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Emanuela F
authors.initials: EF
authors.lastname: Craparo
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sezione di Chimica e Tecnologie Farmaceutiche, Università di Palermo, via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Sardo
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sezione di Biologia Cellulare, Università di Palermo, viale delle Scienze, edificio 16, 90128 Palermo, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Serio
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sezione di Biologia Cellulare, Università di Palermo, viale delle Scienze, edificio 16, 90128 Palermo, Italy.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Zizzo
authors.affiliation: Istituto per lo Studio dei Materiali Nanostrutturati (ISMN), U.O.S. Palermo, CNR, via Ugo La Malfa, 153, 90146 Palermo, Italy.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Bondì
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sezione di Chimica e Tecnologie Farmaceutiche, Università di Palermo, via Archirafi 32, 90123 Palermo, Italy; IBF-CNR, via Ugo La Malfa, 153, 90146 Palermo, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giammona
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sezione di Chimica e Tecnologie Farmaceutiche, Università di Palermo, via Archirafi 32, 90123 Palermo, Italy. Electronic address: gennara.cavallaro@unipa.it.
authors.forename: Gennara
authors.initials: G
authors.lastname: Cavallaro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D005029:Ethylenediamines / Q000737:chemistry*; D005260:Female; D005690:Galactose / Q000737:chemistry*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008823:Micelles; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010455:Peptides / Q000737:chemistry*; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D011091:Polyesters / Q000737:chemistry*; D000077157:Sorafenib; D013154:Spleen / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005029:Ethylenediamines; D008823:Micelles; D010455:Peptides; D010671:Phenylurea Compounds; D011091:Polyesters; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); D009536:Niacinamide; C033616:poly(lactide); C031234:ethylenediamine; D000077157:Sorafenib; D005690:Galactose
keywords: Active targeting; Galactosylation; Hepatic cell-targeted carriers; Polymeric micelles