Tocol modified glycol chitosan for the oral delivery of poorly soluble drugs.
The aim of this study was to develop tocol derivatives of chitosan able (i) to self-assemble in the gastrointestinal 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 μg 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.
Université catholique de Louvain, Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Avenue Mounier, 73, B1.73.12, 1200 Brussels, Belgium. nicolas.duhem@uclouvain.be
Nicolas
N
Duhem
Julien
J
Rolland
Raphaël
R
Riva
Pierre
P
Guillet
Jean-Marc
JM
Schumers
Christine
C
Jérome
Jean-François
JF
Gohy
Véronique
V
Préat
D000284:Administration, Oral; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D007654:Ketoconazole / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008823:Micelles; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010539:Permeability; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D024505:Tocopherols / Q000737:chemistry* / Q000633:toxicity
D004337:Drug Carriers; D008823:Micelles; C118638:glycol-chitosan; D017964:Itraconazole; D048271:Chitosan; D024505:Tocopherols; D007654:Ketoconazole