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.
Publication types
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Evaluation Study
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antineoplastic Agents* / chemistry
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Antineoplastic Agents* / therapeutic use
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Biocompatible Materials / chemistry
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Biocompatible Materials / metabolism
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Camptothecin / analogs & derivatives*
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Camptothecin / chemistry
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Camptothecin / therapeutic use
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Cell Line, Tumor
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Colonic Neoplasms / drug therapy*
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Drug Carriers / chemistry
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Drug Carriers / metabolism
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Drug Delivery Systems / methods
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Female
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Humans
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Male
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Materials Testing
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Methacrylates* / chemistry
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Methacrylates* / metabolism
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Mice
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Mice, Nude
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Molecular Structure
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Neoplasm Transplantation
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Polymers* / chemistry
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Polymers* / metabolism
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Survival Rate
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Transplantation, Heterologous*
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Xenograft Model Antitumor Assays / methods*
Substances
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Antineoplastic Agents
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Biocompatible Materials
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Drug Carriers
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Methacrylates
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Polymers
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9-aminocamptothecin
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hydroxypropyl methacrylate
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Camptothecin