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

George Mattheolabakis, Gerardo Mackenzie, Liqun Huang, Nengtai Ouyang, Ka Wing Cheng, Basil Rigas

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1471-1482
Number of pages12
JournalPharmaceutical Research
Volume30
Issue number6
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Fingerprint

Sulindac
Experimental Arthritis
Hydrogel
Arthritis
Pharmacokinetics
Rats
Poloxamer
Freund's Adjuvant
Cartilage
Locomotion
Bone Resorption
Interleukin-10
Interleukin-6
Bone
Joints
Chemical activation
Inflammation
Plasmas
Topical Administration
Therapeutics

Keywords

  • arthritis
  • hydrogel
  • NSAIDs
  • phospho-sulindac
  • transdermal

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Topically applied phospho-sulindac hydrogel is efficacious and safe in the treatment of experimental arthritis in rats. / Mattheolabakis, George; Mackenzie, Gerardo; Huang, Liqun; Ouyang, Nengtai; Cheng, Ka Wing; Rigas, Basil.

In: Pharmaceutical Research, Vol. 30, No. 6, 01.06.2013, p. 1471-1482.

Research output: Contribution to journalArticle

Mattheolabakis, George ; Mackenzie, Gerardo ; Huang, Liqun ; Ouyang, Nengtai ; Cheng, Ka Wing ; Rigas, Basil. / Topically applied phospho-sulindac hydrogel is efficacious and safe in the treatment of experimental arthritis in rats. In: Pharmaceutical Research. 2013 ; Vol. 30, No. 6. pp. 1471-1482.
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