title: Physico-chemical characterization of polymeric micelles loaded with platinum derivatives by capillary electrophoresis and related methods.
abstract: (1,2-diamino-cyclohexane)Platinum(II) ((DACH)Pt) loaded polymeric micelles of poly(ethylene glycol-b-sodium glutamate) (PEG-b-PGlu) are currently studied as a potential candidate to replace oxaliplatin in the treatment of cancers with the aim to reduce side effects like cumulative peripheral distal neurotoxicity and acute dysesthesias. As for all synthetic polymeric drug delivery systems, the characterization of the (co)polymer precursors and of the final drug delivery system (polymeric micelles) is crucial to control the repeatability of the different batches and to get correlation between physico-chemical structure and biological activity. In this work, the use of capillary electrophoresis (CE) and related methods for the characterization of (DACH)Pt-loaded polymeric micelles and their precursor (PEG-b-PGlu copolymer) has been investigated in detail. The separation and quantification of residual PGlu homopolymer in the PEG-b-PGlu sample were performed by free solution capillary zone electrophoresis mode. This mode brought also information on the PEG-b-PGlu copolymer composition and polydispersity. It also permitted to monitor the decomposition of polymeric micelles in the presence of NaCl at room temperature. Interactions between PEG-b-PGlu unimers, on one hand, and polymeric micelles or surfactants, on the other hand, were studied by using the Micellar Electrokinetic Chromatography and Frontal Analysis Capillary Electrophoresis modes. Finally, weight-average hydrodynamic radii of the loaded polymeric micelles and of the PEG-b-PGlu unimers were determined by Taylor Dispersion Analysis (an absolute size determination method that can be easily implemented on CE apparatus).
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM, UMR 5247 CNRS-Université de Montpellier1-Université de Montpellier 2), Place Eugène Bataillon, 34095 Montpellier Cedex 5, France.
authors.forename: Farid
authors.initials: F
authors.lastname: Oukacine
authors.affiliation: Debiopharm International SA, Espace «après-demain», EPFL, Innovation Park, Lausanne 1015, Switzerland.
authors.forename: Stephane
authors.initials: S
authors.lastname: Bernard
authors.affiliation: Nanocarrier, Chuou 144-15, 226-39 Wakashiba, Kashiwa, Chiba, 277-0871, Japan.
authors.forename: Iulian
authors.initials: I
authors.lastname: Bobe
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM, UMR 5247 CNRS-Université de Montpellier1-Université de Montpellier 2), Place Eugène Bataillon, 34095 Montpellier Cedex 5, France. Electronic address: hcottet@univ-montp2.fr.
authors.forename: Hervé
authors.initials: H
authors.lastname: Cottet
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D053801:Capillary Electrochromatography; D016503:Drug Delivery Systems; D008823:Micelles; D053758:Nanoparticles; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D017671:Platinum Compounds / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols; D011108:Polymers / Q000737:chemistry*; D012965:Sodium Chloride; D012970:Sodium Glutamate
chemical_list: C554217:((1R,2R)-1,2-diaminocyclohexane)platinum(II); D000970:Antineoplastic Agents; D008823:Micelles; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D011108:Polymers; D011092:Polyethylene Glycols; D012965:Sodium Chloride; D012970:Sodium Glutamate
keywords: Cancer; Capillary electrophoresis; Nanoparticles; Oxaliplatin; Polymeric micelles