AACR Annual Meeting Presentation
11, May 2015
The antitumor activity of hyaluronic acid nimesulide-NH2 bioconjugate (CA102N) in human colorectal cancer (CRC)
Tuesday, Apr 21, 2015, 1:00 PM - 5:00 PM
Poster Board Number:
Eskouhie Tchaparian. HolyStone Healthcare, Taipei, Taiwan
Carrier mediated drug delivery systems are promising next generation therapeutics for targeted delivery and improved efficacy and safety of cytotoxic drugs. Hyaluronic Acid conjugated drugs (HACD) are novel carrier-mediated drug delivery systems (Targeting Carrier™) characterized by CD44-mediated endocytosis of Hyaluronic Acid (HA) and intracellular drug release. The present study investigates the in vitro and in vivo antitumor activity of CA102N, an HA- Cyclooxygenase-2 inhibitor conjugate, HA-Nimesulide, currently in preclinical development. Cyclooxygenase-2 (COX-2) inhibitors are a class of compounds that are associated with anticancer properties. CA102N was able to selectively inhibit HCT116 and HT29, CRC cancer cell growth in vitro with an IC50 of 57.7 and 77.14 μM respectively. In in vivo studies, strong anti-tumor effects and rapid tumor shrinkage was observed within 3 days posttherapy in mice bearing HT-29 xenografts treated with either 1.5 or 4.5 mg/kg of relative amount of the conjugate. Further, full and sustained regression of tumors was also attained during the entire observational period (14 days) after the last dose. No treatment related toxicity was noticed in mice. HACD drug delivery systems may offer great advantages in the development of a new class of bioconjugated drugs for intracellular delivery and enhanced safety of potent cytotoxic drugs.