Improvement in the efficacy of dexketoprofen by its prodrug in lipid emulsion



A lipid emulsion delivery system was developed to improve the anti-inflammatory and anti-nociceptive activities of dexketoprofen. The dexketoprofen isopropyl ester (DE) lipid emulsion (DEE) with a particle size of 208.1 ± 33.1 nm and a charge of −34.81 mV was administered to rats and then compared with dexketoprofen injection solution (DS). There was no statistical significance in their pharmacokinetic parameters. The anti-inflammatory effect of DEE was evaluated by experiments involving egg-albumin-induced paw edema in rats and xylene-induced ear swelling in mice. In the paw edema test, the swelling of the DEE group recovered quickly from 1 to 3 h (p<0.05), compared with the DS group. In the ear swelling test, the inhibition rate produced by DEE and DS was 57.79 and 28.57%, respectively. Acetic acid-induced abdominal constriction and hot-plate experiments were used to evaluate the peripheral and central anti-nociceptive actions of DEE. In the acetic acid-induced abdominal constriction test, DEE significantly restrained the writhing responses with a pain inhibition rate of 66.38% compared with 30.06% for the DS group. In the hot-plate test, both preparations had a similar pain threshold increasing percentage. This study shows that the anti-inflammatory and anti-nociceptive activities of dexketoprofen are markedly improved after incorporation into a lipid emulsion.

Practical applications: Dexketoprofen is an important drug for the management of inflammation and treatment of pain. However, its commercial preparations have usually been applied to treat diseases which are less serious because of their limited efficiencies. In this study, the anti-inflammatory and anti-nociceptive activities of dexketoprofen are markedly improved by incorporating its prodrug into the lipid emulsion. Therefore, the lipid emulsion preparation can be used to treat more kinds of inflammation and pain in clinic.