Comparative assessment of effectiveness of ketoprofen and ketoprofen/beta-cyclodextrin complex in two experimental models of inflammation in rats

Abstract

Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) can lead to adverse effects such as gastrointestinal distress. The complexation of different groups of active substances with b-cyclodextrin (b-CD) has drawn considerable interest over recent years. The purpose of this study was to analyze the ketoprofen/b-cyclodextrin (K/b-CD) conjugate complex as well as to assess its anti-inflammatory effect after oral administration (doses of 30 mg/m2 and 15 mg/m2 of body surface), compared with ketoprofen. The studies were done on two models of experimentally-induced acute inflammation in rats (n ¼ 48, 6/group), by means of intraplantar administration of a 10% aqueous kaolin suspension and intraperitoneal administration of a 1% sodium thioglycolate solution. The dynamics of the acute inflammatory process and the anti-inflammatory effects were monitored using plethysmometric determinations after 3, 6, 9, 12, 24 and 48 h (plantar inflammation), and the absorbance of the exudates (spectrophotometrically read) and nucleated cell counts after 24 h (peritoneal inflammation). The coupling of ketoprofen with b-CD resulted in increased solubility (100% in 60 min) of the newly-formed product, which further resulted in a higher bioavailability compared with ketoprofen (<40% in 120 min). In both models of experimentally-induced inflammation, the K/b-CD complex had a higher anti-inflammatory activity than ketoprofen.