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Antitumor Efficacy of Colon‐Specific HPMA Copolymer/9‐Aminocamptothecin Conjugates in Mice Bearing Human‐Colon Carcinoma Xenografts |
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| Authors: | Song‐Qi Gao Yongen Sun Pavla Kopečková C Matthew Peterson Jindřich Kopeček |
| Institution: | 1. Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, Utah 84112, USA;2. Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah 84112, USA;3. Department of Bioengineering, University of Utah, Salt Lake City, Utah 84112, USA;4. Center for Controlled Chemical Delivery, 20 S 2030 E, BPRB 205B, University of Utah, Salt Lake City, UT 84112‐9452, USA |
| Abstract: | The antitumor activity of a colon‐specific N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymer – 9‐aminocamptothecin (9‐AC) conjugate (P‐9‐AC) was assessed in orthotopic and subcutaneous animal (HT29 xenograft) tumor models. P‐9‐AC treatment of mice bearing orthotopic colon tumors, with a dose of 3 mg/kg of 9‐AC equivalent every other day for 6 weeks, resulted in regression of tumors in 9 of 10 mice. A lower dose of P‐9‐AC (1.25 mg/kg of 9‐AC equivalent) every other day for 8 weeks inhibited subcutaneous tumor growth in all mice. No liver metastases were observed. Colon‐specific release of 9‐AC from polymer conjugates enhanced antitumor activity and minimized the systemic toxicity.  |
| Keywords: | antitumor efficacy colon‐specific drug delivery HPMA‐copolymer/9‐aminocamptothecin conjugate human‐colon carcinoma xenografts |