Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 38, Issue 12, Pages 1918-1924Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b15-00567
Keywords
nanoparticle; ketoprofen; gel ointment; drug delivery; adjuvant-induced arthritis
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Funding
- Grants-in-Aid for Scientific Research [15K08115] Funding Source: KAKEN
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We previously reported that dermal application using nanoparticles improves skin penetration. In this study, we prepared novel topical formulations containing ketoprofen (KET) solid nanoparticles (KETnano gel ointment) and investigated the antiinflammatory effect of the KET nanoparticle formulations on rheumatoid arthritis using adjuvant-induced arthritis (AA) rats. The KETnano 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 83nm. In the in vitro skin penetration experiment, the penetration rate (J(c)) and penetration coefficient through the skin (K-p) values of the KETnano gel ointment were significantly higher than those of gel ointment containing KET microparticles (KETmicro gel ointment; mean particle size 7.7 mu m). 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 KETnano gel ointment were significantly higher than those of rats receiving the KETmicro gel ointment, and the amounts of KET in the skin tissues of rats receiving the KETnano gel ointment were also significantly higher than those of rats receiving the KETmicro gel ointment. In addition, the application of the KETnano gel ointment attenuated the enhancement of paw edema of the hind feet of AA rats more than the application of the KETmicro gel ointment. Our findings suggest that a topical drug delivery system using nanoparticles could lead to expansion in the therapeutic use of KET.
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