Pharmaceutical Nanotechnology Tocol modified glycol chitosan for the oral delivery of poorly soluble drugs.

Nicolas Duhem , Raphael Riva (1) , Pierre Guillet (2) , Jean-Marc Schumers , Christine Jérome (3) , Jean-François Gohy (4) , Véronique Préat (5)

1 Center for Education and Research on Macromolecules
2 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
3 CERM
4 UCL - Université Catholique de Louvain = Catholic University of Louvain
5 Unité de pharmacie galénique, industrielle et officinale

The aim of this study was to develop tocol derivatives of chitosan able (i) to self-assemble in the gastroin-testinal tract and (ii) to enhance the solubility of poorly soluble drugs. Among the derivatives synthesized, tocopherol succinate glycol chitosan (GC-TOS) conjugates spontaneously formed micelles in aqueous solution with a critical micelle concentration of 2 ␮g mL −1. AFM and TEM analysis showed that spherical micelles were formed. The GC-TOS increased water solubility of 2 model class II drugs. GC-TOS loading efficiency was 2.4% (w/w) for ketoconazole and 0.14% (w/w) for itraconazole, respectively. GC-TOS was non-cytotoxic at concentrations up to 10 mg mL −1. A 3.4-fold increase of the apparent permeation coefficient of ketoconazole across a Caco-2 cell monolayer was demonstrated. Tocol polymer conjugates may be promising vehicles for the oral delivery of poorly soluble drugs.

Domaines: Chimie

Nicolas Duhem, Raphael Riva, Pierre Guillet, Jean-Marc Schumers, Christine Jérome, et al.. Pharmaceutical Nanotechnology Tocol modified glycol chitosan for the oral delivery of poorly soluble drugs.. International Journal of Pharmaceutics, 2012, ⟨10.1016/j.ijpharm.2011.12.010⟩. ⟨hal-01332191⟩