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Pharm Res. 2013 Jun;30(6):1471-82. doi: 10.1007/s11095-012-0953-8. Epub 2013 Mar 13.

Topically applied phospho-sulindac hydrogel is efficacious and safe in the treatment of experimental arthritis in rats.

Author information

1
Division of Cancer Prevention, Department of Medicine, Stony Brook University, HSC T17-080, Stony Brook, New York 11794-8173, USA.

Abstract

PURPOSE:

Formulate phospho-sulindac (P-S, OXT-328) in a Pluronic hydrogel to be used as a topical anti-inflammatory agent and study its efficacy, safety and pharmacokinetics in an arthritis model.

METHODS:

LEW/crlBR rats with Freund's adjuvant-induced arthritis were treated with P-S formulated in Pluronic hydrogel (PSH). We determined the clinical manifestations of arthritis including the locomotor activity of the rats; evaluated joints for inflammation, bone resorption, cartilage damage, COX-2 expression and NF-κB activation; assayed plasma IL-6 and IL-10 levels; and studied the pharmacokinetics of P-S in rats after topical or oral administration.

RESULTS:

PSH applied at the onset of arthritis or when arthritis was fully developed, suppressed it by 56-82%, improved the locomotor activity of the rats 2.1-4.4 fold, suppressed synovial inflammation, bone resorption, cartilage damage, NF-κB activation and COX-2 expression but not plasma IL-6 and IL-10 levels. There were no side effects. PSH produced rapidly high local levels of P-S with <14% of P-S reaching the circulation, while orally administered P-S was rapidly metabolized generating much lower joint levels of P-S.

CONCLUSIONS:

Topical application of PSH is efficacious and safe in the treatment of Freund's adjuvant-induced arthritis; has a favorable pharmacokinetic profile; and likely acts by suppressing key pro-inflammatory signaling pathways.

PMID:
23483440
PMCID:
PMC4395004
DOI:
10.1007/s11095-012-0953-8
[Indexed for MEDLINE]
Free PMC Article

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