title: Antitumor efficacy of colon-specific HPMA copolymer/9-aminocamptothecin conjugates in mice bearing human-colon carcinoma xenografts.
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.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Song-Qi
authors.initials: SQ
authors.lastname: Gao
authors.forename: Yongen
authors.initials: Y
authors.lastname: Sun
authors.forename: Pavla
authors.initials: P
authors.lastname: Kopecková
authors.forename: C Matthew
authors.initials: CM
authors.lastname: Peterson
authors.forename: Jindrich
authors.initials: J
authors.lastname: Kopecek
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D015996:Survival Rate; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D008689:Methacrylates; D011108:Polymers; C080125:9-aminocamptothecin; C032802:hydroxypropyl methacrylate; D002166:Camptothecin
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