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 (∼ 1% w/w) and its rapid release from nanoparticles. These experiments constituted an essential step for the development of busulphan-loaded long-circulating nanospheres.