Cyclomaltoheptaose mixed esters of anti-inflammatory drugs and short-chain fatty acids and study of their enzymatic hydrolysis in vitro

In an effort to enhance the drug-loading capacity of cyclomaltoheptaose (β-cyclodextrin, βCD) and to combine the function of anti-inflammatory drugs with short-chain fatty acids (SCFA), ternary esters incorporating seven copies of an anti-inflammatory drug and 14 copies of a SCFA onto a β-cyclodextrin core were designed and prepared. Acetic, propionic, or butyric esters were introduced at secondary OH groups, and ibuprofen, flurbiprofen, or felbinac was attached to primary OH groups through ester bonds. Heptakis[2,3-di-O-butanoyl-6-O-2-(biphenyl-4-yl)-ethanoyl]-cyclomaltoheptaose was very stable in aqueous and esterase solution. It was hydrolyzed by α-amylase (4 units/mL) with t1/2 value of 18 h. The total released amount of biphenyl acetic acid was 38% after 24 h when the esterase was added after the α-amylase hydrolysis. The present results suggest that these nine βCD conjugates may release the anti-inflammatory drug in the colonic contents.