title: Assessment of celecoxib poly(lactic-co-glycolic) acid nanoformulation on drug pharmacodynamics and pharmacokinetics in rats.
abstract: Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP).
  
  
  
  Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP). Plasma and urine (over 12 hrs) samples were collected prior to and post-treatment. The mean percent change from baseline of urine flow rate along with electrolyte concentrations in plasma and urine were assessed based on 100 g body weight. Using tissues collected 24 hrs post-treatment, gastrointestinal inflammation was estimated through duodenal and gastric prostaglandin E2 (PGE2) and duodenal myeloperoxidase (MPO) levels; while kidney tissue was examined for dilatation and necrosis. CEL concentration was assayed in renal tissue and plasma utilizing high-performance liquid chromatography.
  
  
  
  Although there were significant changes when comparing CEL and CEL-NP to VEH in plasma sodium concentration and potassium excretion rate, there was no significant variation between CEL and CEL-NP. There was a significant reduction of protective duodenal PGE2 in CEL compared to VEH (p = 0.0088) and CEL-NP (p = 0.02). In the CEL-NP formulation, t1/2, Cmax, AUC0-∞, and Vd/F increased significantly when compared to CEL.
  
  
  
  At the observed dosage and duration, CEL-NP may not affect CEL-associated electrolyte parameters in either plasma or urine; however, it does provide increased systemic exposure while potentially alleviating some gastrointestinal outcomes related to inflammation.
authors.affiliation: Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN, USA. harirfor@etsu.edu.
authors.forename: S
authors.initials: S
authors.lastname: Harirforoosh
authors.forename: K O
authors.initials: KO
authors.lastname: West
authors.forename: D E
authors.initials: DE
authors.lastname: Murrell
authors.forename: J W
authors.initials: JW
authors.lastname: Denham
authors.forename: P C
authors.initials: PC
authors.lastname: Panus
authors.forename: G A
authors.initials: GA
authors.lastname: Hanley
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000068579:Celecoxib / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006018:Glycols; D011091:Polyesters; D051381:Rats
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006018:Glycols; D011091:Polyesters; C033616:poly(lactide); D000068579:Celecoxib