Celecoxib coupled to dextran via a glutamic acid linker yields a polymeric prodrug suitable for colonic delivery

Yonghyun Lee, Jungyun Kim, Wooseong Kim, Joon Nam, Seongkeun Jeong, Sunyoung Lee, Jin Wook Yoo, Min Soo Kim, Yunjin Jung

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Celecoxib, a selective cyclooxygenase-2 inhibitor, is potentially useful for the treatment of colonic diseases such as colorectal cancer and colitis. However, the cardiovascular toxicity of celecoxib limits its routine use in the clinic. Generally, colon-specific delivery of a drug both increases the therapeutic availability in the large intestine and decreases the systemic absorption of the drug, most likely resulting in enhanced therapeutic effects against colonic diseases such as colitis and reduced systemic side effects. To develop a colon-specific prodrug of celecoxib that could reduce its cardiovascular toxicity and improve its therapeutic activity, dextran–glutamic acid–celecoxib conjugate (glutam-1-yl celecoxib-dextran ester [G1CD]) was prepared and evaluated. While stable in pH 1.2 and 6.8 buffer solutions and small-intestinal contents, G1CD efficiently released celecoxib in cecal contents. Oral administration of G1CD to rats delivered a larger amount of celecoxib to the large intestine than free celecoxib. G1CD prevented the systemic absorption of celecoxib and did not decrease the serum level of 6-ketoprostaglandin F, an inverse indicator of cardiovascular toxicity of celecoxib. Collectively, G1CD may be a polymeric colon-specific celecoxib prodrug with therapeutic and toxicological advantages.

Original languageEnglish
Pages (from-to)4105-4113
Number of pages9
JournalDrug Design, Development and Therapy
Volume9
DOIs
StatePublished - 30 Jul 2015

Keywords

  • Cardiovascular toxicity
  • Celecoxib
  • Colon-specific drug delivery
  • Dextran
  • Prodrug

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