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The current study aims to investigate the effect of chitosan derivatives on the intestinal absorption and bioavailabilities of forsythoside A (FTA) and Chlorogenic acid (CHA), the major active components in  Flos Lonicerae  -  Fructus Forsythiae  herb couple. Biopharmaceutics and pharmacokinetics properties of the two compounds have been characterized  in vitro ,  in situ  as well as in rats. Based on the identified biopharmaceutics characteristics of the two compounds, the effect of chitosan derivatives as an absorption enhancer on the intestinal absorption and pharmacokinetics of FTA and CHA in pure compound form as well as extract form were investigated  in vitr o,  in situ  and  in vivo.  Both FTA and CHA demonstrated very limited intestinal permeabilities, leading to oral bioavailabilities being only 0.50% and 0.13% in rats, respectively. Results from both  in vitro ,  in situ  as well as  in vivo  studies consistently indicated that Chito-oligosaccharide (COS) at dosage of 25 mg/kg could enhance intestinal permeabilities significantly as well as the  in vivo  bioavailabilities of both FTA and CHA than CMCs in  Flos Lonicerae  -  Fructus Forsythiae  herb couple preparations, and was safe for gastrointestine from morphological observation. Besides, treatment with  Flos Lonicerae  -  Fructus Forsythiae  herb couple preparations with COS at the dosage of 25 mg/kg prevented MDCK damage after influenza virus propagation, which was significantly better than control. The current findings not only identified the usefulness of COS for the improved delivery of  Flos Lonicerae  -  Fructus Forsythiae  preparations but also demonstrated the importance of biopharmaceutical characterization in the dosage form development of traditional Chinese medicine.

plos one

Improvement of Intestinal Absorption of Forsythoside A and Chlorogenic Acid by Different Carboxymethyl Chitosan and Chito-oligosaccharide, Application to Flos Lonicerae - Fructus Forsythiae Herb Couple Preparations