Pharmacokinetics and Antiinflammatory Effect of a Novel Gel System Containing Ketoprofen Solid Nanoparticles

抄録

We previously reported that dermal application using nanoparticles improves skin penetration. In this study, we prepared novel topical formulations containing ketoprofen (KET) solid nanoparticles (KET_nano gel ointment) and investigated the antiinflammatory effect of the KET nanoparticle formulations on rheumatoid arthritis using adjuvant-induced arthritis (AA) rats. The KET_nano gel ointment was prepared using a bead mill method and additives including methylcellulose and Carbopol 934; the mean particle size of the KET nanoparticles was 83 nm. In the in vitro skin penetration experiment, the penetration rate (J_c) and penetration coefficient through the skin (K_p) values of the KET_nano gel ointment were significantly higher than those of gel ointment containing KET microparticles (KET_micro gel ointment; mean particle size 7.7 µm). On the other hand, in the in vivo percutaneous absorption experiment, the apparent absorption rate constant (k_a) and the areas under the KET concentration–time curve values in the skin of rats receiving the KET_nano gel ointment were significantly higher than those of rats receiving the KET_micro gel ointment, and the amounts of KET in the skin tissues of rats receiving the KET_nano gel ointment were also significantly higher than those of rats receiving the KET_micro gel ointment. In addition, the application of the KET_nano gel ointment attenuated the enhancement of paw edema of the hind feet of AA rats more than the application of the KET_micro gel ointment. Our findings suggest that a topical drug delivery system using nanoparticles could lead to expansion in the therapeutic use of KET.