Glucosamine, as a dietary supplement for management of osteoarthritis, has a low and erratic oral bioavailability due to its transport-mediated absorption and presystemic loss in liver and GI tract. The present study described an effective approach to improve glucosamine intestinal absorption and hence its bioavailability using chitosan. Effects of chitosan on intestinal permeability and pharmacokinetics of glucosamine were evaluated in Caco-2 cell monolayer and rats, respectively. In addition, randomized crossover pharmacokinetic studies in beagle dogs were performed to evaluate the oral bioavailabilities of the developed glucosamine oral formulations containing chitosan (QD-Glu solution and QD-Glu tablet) in comparison to its commercial products. Caco-2 permeability studies demonstrated that chitosan could enhance the absorptive transport of glucosamine by 1.9-4.0-fold via the reversible opening of the cell tight junction. After oral administration of glucosamine solutions containing chitosan in rats, it was found that 0.5% (w/v) chitosan exhibited the highest enhancement in Cmax (2.8-fold) and AUC0-∞ (2.5-fold) of glucosamine. Further pharmacokinetic studies in beagle dogs demonstrated that QD-Glu solution and QD-Glu tablet showed much higher relative bioavailabilities of 313% and 186%, when comparing with Wellesse™ solution and Voltaflex™ tablet, respectively. In conclusion, chitosan could serve as a promising oral absorption enhancer for glucosamine.
Keywords: Bioavailability; Caco-2 cell model; Chitosan; Glucosamine; Permeability.
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