Disposition of human recombinant lubricin in naive rats and in a rat model of post-traumatic arthritis after intra-articular or intravenous administration.

Methods Development
Other

Abstract

We have recently demonstrated that intra-articular (IA) administration of human recombinant lubricin, LUB:1, significantly inhibited cartilage degeneration and pain in the rat meniscal tear model of post-traumatic arthritis. In this report, we show that after a single IA injection to naïve rats and rats that underwent unilateral meniscal tear, [(125)I]LUB:1 had a tri-phasic disposition profile, with the alpha, beta, and gamma half-life estimates of 4.5 h, 1.5 days, and 2.1 weeks, respectively. We hypothesize that the terminal phase kinetics was related to [(125)I]LUB:1 binding to its ligands. [(125)I]LUB:1 was detected on articular cartilage surfaces as long as 28 days after single IA injection. Micro-autoradiography analysis suggested that [(125)I]LUB:1 tended to localize to damaged joint surfaces in rats with meniscal tear. After a single intravenous (IV) dose to rats, [(125)I]LUB:1 was eliminated rapidly from the systemic circulation, with a mean total body clearance of 154 mL/h/kg and a mean elimination half-life (t (1/2)) of 6.7 h. Overall, LUB:1 has met a desired disposition profile of a potential therapeutic intended for an IA administration: target tissue (knee) retention and fast elimination from the systemic circulation after a single IA or IV dose.

Authors

Vugmeyster, Yulia; Wang, Qin; Xu, Xin; Harrold, John; Daugusta, Daren; Li, Jian; Zollner, Richard; Flannery, Carl R; Rivera-Bermúdez, Moisés A;

Keywords

  • Animals
  • Arthritis, Experimental/ drug therapy
  • Arthritis, Experimental/ pathology
  • Autoradiography/ methods
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Female
  • Glycoproteins/ administration & dosage
  • Glycoproteins/ pharmacokinetics
  • Glycoproteins/ pharmacology
  • Half-Life
  • Humans
  • Injections, Intra-Articular
  • Injections, Intravenous
  • Knee Joint/ drug effects
  • Knee Joint/ pathology
  • Male
  • Rats
  • Rats, Inbred Lew
  • Recombinant Proteins
  • Time Factors
  • Tissue Distribution

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