Busulphan-loaded long-circulating nanospheres, a very attractive challenge for both galenists and pharmacologists.
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.
Bouligand
Jerome
J
CNRS & Université Paris XI, Pharmacotechnie, BiopharmacieChatenay Malabry, France.
Couvreur
Patrick
P
Layre
Anne M
AM
Deroussent
Alain
A
Paci
Angelo
A
Delain
Etienne
E
Vassal
Gilles
G
Gref
Ruxandra
R
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*
D018906:Antineoplastic Agents, Alkylating; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D011092:Polyethylene Glycols; D002066:Busulfan