期刊
NANOMEDICINE
卷 6, 期 10, 页码 1683-1695出版社
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.11.69
关键词
busulfan; cytotoxicity; drug crystallization; drug loading; drug release; iron (III) carboxylate; nanoparticle; NMR; porous MOF
资金
- CNRS
- Universite Paris Sud
- Universite de Versailles Saint-Quentin
- Universite Montpellier 2 (Region Languedoc Roussillon)
- Nanogalenic (Region Ile de France and Hauts de Seine)
- EU [ITN 237962, ERC-2007-209241-BioMOFs]
Busulfan is an alkylating agent widely used in chemotherapy, but with severe side effects. Many attempts have been made to entrap busulfan in nanocarriers to avoid liver accumulation and to protect it against rapid degradation in aqueous media. However, poor loadings (<= 5 wt%) and fast release were generally obtained due to the low affinity of busulfan towards the nanocarriers. Moreover, drug crystallization often occurred during nanoparticle preparation. To circumvent these drawbacks, metal organic framework (MOF) nanoparticles, based on crystalline porous iron (III) carboxylates, have shown an unprecedented loading (up to 25 wt%) of busulfan. This was attributed to the high porosity of nanoMOFs as well as to their hydrophilic-hydrophobic internal microenvironment well adapted to the amphiphilic character of busulfan. NanoMOFs formulations have kept busulfan in molecular form, preventing its crystallization and degradation. Indeed, busulfan was released intact, as proved by the maintenance of its pharmacological activity.
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