Procyanidins (PAs) are polyphenols in plant food that have many health benefits, including cancer prevention, cardiovascular protection and diabetes prevention. PAs have been known to have low oral bioavailability. In this review, we summarize the published results on the ADME (absorption, distribution, metabolism and excretion) of PAs in vivo and in vitro. After oral administration, in the stomach the decomposition of PAs is highly dependent on the pH value of gastric juice, which is also affected by food intake. In the small intestine, PA polymers and oligomers with DP > 4 are not directly absorbed in vivo, but minor PA monomers and dimers could be detected in the plasma. Methylated and glucuronidated PA dimers and monomers are the main metabolites of PAs in plasma. In the colon, PAs are catabolized by colonic microflora into a series of low molecular weight phenolic acids, such as phenyl valerolactone, phenylacetic acids and phenylpropionic acids. We reviewed the degradation of PAs in gastric digestion, the absorption of PAs in the small intestine and the metabolic pathway of PAs by colonic microflora. To clearly explain the in vivo pharmacokinetics of PAs, a systematic comparative analysis on previously published data on PAs was conducted.

No abstract

No abstract

Inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis is a chronic autoimmune disease affecting nearly five million people worldwide. Among all drug delivery system, oral administration is the most preferable route for colon-specific targeting and the treatment of IBD. Herein, an amphiphilic curcumin polymer (PCur) composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic curcumin (Cur) linked by disulfide bond was synthesized and characterized. The sufficient solubility, nano-scaled size and close to the neutral surface potential of PCur lead to preferential accumulation of the active drug in the inflamed regions of the gut. Moreover, PCur showed limited drug release and enhanced robustness under the physiological pH of the gastrointestinal tract (GIT), and a significantly elevated release was observed when responding to a bacterial reduction in the colon. Furthermore, cellular studies confirmed PCur had low cytotoxicity and increased transmembrane permeability, resulting in improved oral bioavailability evidenced by in vivo pharmacokinetics of rats. Finally, with DSS-induced murine model of IBD, we demonstrated that orally administered PCur ameliorated the inflammatory progression in the colon and could protect mice from IBD. In conclusion, it is illustrated that the developed PCur conjugate could potentially be employed as a colon-specific candidate for IBD treatment.

No abstract