title: Busulphan-loaded long-circulating nanospheres, a very attractive challenge for both galenists and pharmacologists.
abstract: Hepatic veino-occlusive disease (HVOD) is the most severe and frequent busulphan high risk injury. The development of busulphan-loaded'stealth'nanospheres which avoid liver accumulation should minimize busulphan toxicity. To reach this important goal, this study has attempted to develop poly(ethylene glycol) (PEG)-coated nanospheres using polyester-PEG diblock copolymers and studied the busulphan physico-chemical characteristics related to its encapsulation. Nanospheres were prepared by nanoprecipitation and by emulsion-solvent evaporation techniques. They were characterized by microscopy and dynamic light-scattering. Busulphan interactions with adjuvants were studied using gas chromatography and mass spectrometry, high performance thin-layer chromatography and dynamic scanning calorimetry. These investigations explain both the low busulphan loadings obtained ( approximately 1% w/w) and its rapid release from nanoparticles. These experiments constituted an essential step for the development of busulphan-loaded long-circulating nanospheres.
authors.affiliation: CNRS & Université Paris XI, Pharmacotechnie, BiopharmacieChatenay Malabry, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Bouligand
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Anne M
authors.initials: AM
authors.lastname: Layre
authors.forename: Alain
authors.initials: A
authors.lastname: Deroussent
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
authors.forename: Etienne
authors.initials: E
authors.lastname: Delain
authors.forename: Gilles
authors.initials: G
authors.lastname: Vassal
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gref
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D002066:Busulfan / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D011092:Polyethylene Glycols; D002066:Busulfan