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(epsilon-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). (3)H-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.
UMR CNRS 8612, Faculty of Pharmacy, Paris-Sud University, 5 rue Jean Baptiste Clément, 92296 Châtenay-Malabry, France.
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Layre
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Couvreur
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Chacun
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Richard
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Passirani
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Requier
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JP
Benoit
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Gref
D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D002066:Busulfan / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D015941:Complement Hemolytic Activity Assay; D003487:Cyanoacrylates; D004337:Drug Carriers / Q000737:chemistry*; D004659:Enbucrilate; D005027:Ethylene Oxide; D005612:Freeze Drying; D007783:Lactones; D053758:Nanoparticles; D011108:Polymers; D012995:Solubility; D013052:Spectrometry, X-Ray Emission; D013499:Surface Properties; D013678:Technology, Pharmaceutical
D018906:Antineoplastic Agents, Alkylating; D003487:Cyanoacrylates; D004337:Drug Carriers; D007783:Lactones; C400421:PLC(20)-b-PEO(44); D011108:Polymers; D004659:Enbucrilate; D002066:Busulfan; D005027:Ethylene Oxide