Novel composite core-shell nanoparticles as busulfan carriers

This study presents a method for the design of novel composite core-shell nanoparticles able to encapsulate busulfan, a crystalline drug. They were obtained by co-precipitation of mixtures of poly(isobutylcyanoacrylate) (PIBCA) and of a diblock copolymer, poly(ε-caprolactone)–poly(ethylene glycol) (PCL–PEG), in different mass ratios. The nanoparticle size, morphology and surface charge were assessed. The chemical composition of the top layers was determined by X-ray photo-electron spectroscopy (XPS). 3H-labelled busulfan was used in order to determine the drug loading efficiency and the in vitro drug release by liquid scintillation counting. Physico-chemical techniques such as Zeta potential determination and XPS analysis provided evidence about a preferential surface distribution of the PCL–PEG polymer. Therefore, composite nanoparticles have a ‘core-shell’-type structure, where the “core” is essentially formed by the PIBCA polymer and the “shell” by the PCL–PEG copolymer. The use of PIBCA to form the core of the nanoparticles leads to a 2–4 fold drug loading increase, in comparison to the single PCL–PEG nanoparticles. In addition, the complement activation results showed a significant difference between the composite nanoparticles and the single PIBCA nanoparticles, thus demonstrating that PEG at the surface of the nanoparticles reduced the complement consumption. The PIBCA:PCL–PEG composite nanoparticles prepared using the new co-precipitation method here described represent an original approach for busulfan administration.