title: Porous metal organic framework nanoparticles to address the challenges related to busulfan encapsulation.
abstract: 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.
authors: Faculté de Pharmacie (UMR CNRS 8612), Université Paris-Sud, 92296 Châtenay-Malabry Cedex, France.
authors: T
authors: T
authors: Chalati
authors: P
authors: P
authors: Horcajada
authors: P
authors: P
authors: Couvreur
authors: C
authors: C
authors: Serre
authors: M
authors: M
authors: Ben Yahia
authors: G
authors: G
authors: Maurin
authors: R
authors: R
authors: Gref
mesh_terms: D002066:Busulfan / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry; D016062:Porosity
chemical_list: D004337:Drug Carriers; D009942:Organometallic Compounds; D004364:Pharmaceutical Preparations; D002066:Busulfan