title: Fluorinated and pegylated polyaspartamide derivatives to increase solubility and efficacy of Flutamide.
abstract: New fluorinated amphiphilic copolymers based on a biocompatible polyaspartamide have been prepared in order to obtain polymeric micelles useful for delivering anticancer drugs. In particular, α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) has been derivatized with polyethylene glycol (PEG(2000)) and ethylendiamine (EDA). Both these portions form the hydrophilic part of the copolymer, while the hydrophobic moiety is given by 1,2,4-oxadiazoles: 5-pentafluorophenyl-3-perfluoroheptyl-1,2,4-oxadiazole (PPOX) or 3-carboxyethyl-5-pentadecafluoroheptyl-1,2,4-oxadiazole (CPOX). Copolymers named PHEA-PEG(2000)-EDA-PPOX and PHEA-PEG(2000)-EDA-CPOX have been prepared with various degrees of derivatization and characterized by spectroscopic analyses. Size exclusion chromatography, pyrene colorimetric assay, light scattering analysis and scanning electron microscopy have evidenced the occurrence of a self-association process in aqueous medium. The ability of these aggregates to incorporate a hydrophobic drug and increase its solubility has been evaluated by using Flutamide, a fluorinated anticancer agent. Moreover, the activity of Flutamide-loaded micelles on proliferation of dihydrotestosterone stimulated LNCaP cells has been determined and compared to that of free drug.
authors.affiliation: Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Sezione di Chimica Organica, Università di Palermo, Palermo, Italy.
authors.forename: Antonio Palumbo
authors.initials: AP
authors.lastname: Piccionello
authors.forename: Giovanna
authors.initials: G
authors.lastname: Pitarresi
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
authors.forename: Daniela
authors.initials: D
authors.lastname: Triolo
authors.forename: Pasquale
authors.initials: P
authors.lastname: Picone
authors.forename: Silvestre
authors.initials: S
authors.lastname: Buscemi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giammona
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002850:Chromatography, Gel; D013196:Dihydrotestosterone / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005029:Ethylenediamines / Q000737:chemistry; D005485:Flutamide / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D010069:Oxadiazoles / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D012995:Solubility
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004337:Drug Carriers; D005029:Ethylenediamines; D008823:Micelles; D010069:Oxadiazoles; D010455:Peptides; D011108:Polymers; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); D013196:Dihydrotestosterone; D011092:Polyethylene Glycols; C031234:ethylenediamine; D005485:Flutamide