Synthesis, Characteristics, and Pharmaceutical Properties of Ibuprofen-Cyclodextrin-PEG Conjugate

Abstract

The NSAIDs ibuprofen was chemically conjugated to the PEG-graft-β-CyD with an ester bond and its aqueous solubility was clearly improved. The preliminary release profile of ibuprofen in rat gastrointestinal tract contents was performed at 37°C within 12 hours. The polymeric conjugate almost did not release ibuprofen in the contents of stomach, released ibuprofen only 7.4% in the contents of small intestine, and evidently released ibuprofen up to 58.7% in the contents of colon, respectively. These results demonstrated that the polymeric conjugate was site-specifically biodegraded in the rat colonic contents. On the other hand, the xylene-induced ear swelling technique, the hot plate test, and the brewer's yeast-induced hyperthermia model in mice were performed for evaluating the anti-inflammatory, analgesic, and antipyretic activities of the polymeric conjugate, respectively. The results revealed that the polymeric conjugate maintained a long and stable pharmacodynamic efficiency over a period of 24 hours. Hence, the present polymeric ibuprofen-cyclodextrin-PEG conjugate may be of value as an orally administered long-acting prodrug of ibuprofen through colon-targeting delivery.