Biol Pharm Bull. 2014;37(7):1109-1118.

Effect of Solid Nanoparticle of Indomethacin on Therapy for Rheumatoid Arthritis in Adjuvant-Induced Arthritis Rat

Noriaki Nagai and Yoshimasa Ito*

Faculty of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka, 577-8502, Japan

 

ABSTRACT

We designed new oral formulations containing indomethacin (IMC) solid nanoparticles, and investigate their usefulness by evaluating bioavailability and gastrointestinal lesions. The IMC solid nanoparticles were prepared using methylcellulose (MC), 2-hydroxypropyl-b-cyclodextrin (HPbCD), and the bead mill method, and high quality dispersions containing 1.0% IMC nanoparticles were prepared (IMCnano, particle size: 76 ± 58 nm, means ± S.D.). The fate of serum IMC and the induction of paw edema in adjuvant-induced arthritis (AA) rats receiving low-doses IMCnano (0.4 mg/kg) were similar to those following the administration of a therapeutic dose of conventional IMC prepared with MC and HPbCD (conventional IMC, 2 mg/kg), and the bioavailability in 0.4 mg/kg IMCnano was 5.3-fold higher in comparison with that in 2 mg/kg conventional IMC.IMC-induced gastrointestinal lesions in AA rats administered IMCnano (8 mg/kg), in consideration of bioavailability, were significantly less than for conventional IMC (40 mg/kg). On the other hand, the toxicity caused by conventional IMC and IMCnano was similar in Caco-2 cells. It is possible that the oral administration of IMC solid nanoparticles will show increased effectiveness in treating RA without causing IMC-induced gastrointestinal lesions, since the bioavailability is higher than that of conventional IMC. An oral drug delivery system using drug nanoparticles may expand the usage of NSAIDs for therapy in the inflammatory field.

Keywords: nanoparticle, indomethacin, bioavailability, gastrointestinal lesions, adjuvant-induced arthritis.

PMID:24989003

 

Highlights

  We designed new oral formulations containing indomethacin solid nanoparticles (IMCnano).

  Particle size ofIMCnano is 76 ± 58 nm (means ± S.D.).

  Bioavailability in IMCnano was 5.3-fold higher in comparison with that in conventional indomethacin (oral formulations containing indomethacin microparticles).

  Indomethacin-induced gastrointestinal lesions in adjuvant-induced arthritis rats administered IMCnano (8 mg/kg), in consideration of bioavailability, were significantly less than for conventional IMC (40 mg/kg).

   It is possible that the oral administration of indomethacin nanoparticles will provide increased effectiveness in treating rheumatoid arthritis without the toxicity (gastric and small intestinal ulcerogenic responses to NSAIDs).

 

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