title: On-line capillary electrophoresis-based enzymatic methodology for the study of polymer-drug conjugates.
abstract: This work aims at studying the potentialities of an on-line capillary electrophoresis (CE)-based digestion methodology for evaluating polymer-drug conjugates degradability in the presence of free trypsin (in-solution digestion). A sandwich plugs injection scheme with transverse diffusion of laminar profile (TDLFP) mode was used to achieve on-line digestions. Electrophoretic separation conditions were established using poly-l-Lysine (PLL) as reference substrate. Comparison with off-line digestion was carried out to demonstrate the feasibility of the proposed methodology. The applicability of the on-line CE-based digestion methodology was evaluated for two PLL-drug conjugates and for the four first generations of dendrigraft of lysine (DGL). Different electrophoretic profiles presenting the formation of di, tri, and tetralysine were observed for PLL-drug and DGL. These findings are in good agreement with the nature of the linker used to link the drug to PLL structure and the predicted degradability of DGL. The present on-line methodology applicability was also successfully proven for protein conjugates hydrolysis. In summary, the described methodology provides a powerful tool for the rapid study of biodegradable polymers.
authors.affiliation: Institut des Biomolécules Max Mousseron-IBMM, Centre National de la Recherche Scientifique, Université de Montpellier 1, Université de Montpellier 2, Unité Mixte de Recherche 5247, Faculté de Pharmacie, F-34093, Montpellier cedex 5, France. Electronic address: gaelle.coussot@univ-montp1.fr.
authors.forename: G
authors.initials: G
authors.lastname: Coussot
authors.affiliation: Institut des Biomolécules Max Mousseron-IBMM, Centre National de la Recherche Scientifique, Université de Montpellier 1, Université de Montpellier 2, Unité Mixte de Recherche 5247, Faculté de Pharmacie, F-34093, Montpellier cedex 5, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Ladner
authors.affiliation: Institut des Biomolécules Max Mousseron-IBMM, Centre National de la Recherche Scientifique, Université de Montpellier 1, Université de Montpellier 2, Unité Mixte de Recherche 5247, Faculté de Pharmacie, F-34093, Montpellier cedex 5, France.
authors.forename: C
authors.initials: C
authors.lastname: Bayart
authors.affiliation: Colcom, Cap Alpha, Avenue de l'Europe, F-34830, Clapiers, France.
authors.forename: C
authors.initials: C
authors.lastname: Faye
authors.affiliation: Gemacbio, Lieu-dit Berganton, F-33127, Saint-Jean d'Illac, France.
authors.forename: V
authors.initials: V
authors.lastname: Vigier
authors.affiliation: Institut des Biomolécules Max Mousseron-IBMM, Centre National de la Recherche Scientifique, Université de Montpellier 1, Université de Montpellier 2, Unité Mixte de Recherche 5247, Faculté de Pharmacie, F-34093, Montpellier cedex 5, France.
authors.forename: C
authors.initials: C
authors.lastname: Perrin
mesh_terms: D000818:Animals; D002417:Cattle; D050091:Dendrimers; D004058:Diffusion; D019075:Electrophoresis, Capillary; D006868:Hydrolysis; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D011108:Polymers; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013654:Taurine / Q000737:chemistry; D014357:Trypsin / Q000737:chemistry
chemical_list: D050091:Dendrimers; D004364:Pharmaceutical Preparations; D011108:Polymers; D013654:Taurine; D011107:Polylysine; D012710:Serum Albumin, Bovine; C033952:tetralysine; D014357:Trypsin
keywords: Biodegradable polymers; Capillary electrophoresis; Nano-enzyme reactor; On-line trypsin digestion