Efficacy of PolyMPC–DOX Prodrugs in 4T1 Tumor-Bearing Mice
| Autor: | Xiangji Chen, Todd Emrick, Sallie S. Schneider, Elizabeth M. Henchey, Samantha McRae Page |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Polymers
medicine.medical_treatment Pharmaceutical Science Antineoplastic Agents Pharmacology doxorubicin polymer prodrug Mice In vivo Drug Discovery polycyclic compounds medicine Animals Prodrugs Doxorubicin Mice Inbred BALB C medicine.diagnostic_test polymer−drug conjugate Chemistry Phosphorylcholine Communication Immunogenicity Mammary Neoplasms Experimental Complete blood count Prodrug Xenograft Model Antitumor Assays 3. Good health carbohydrates (lipids) Cytokine drug delivery Drug delivery Molecular Medicine Female poly(methacryloyloxyethyl phosphorylcholine) medicine.drug |
| Zdroj: | Molecular Pharmaceutics |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/mp500009r |
| Popis: | We report the in vivo efficacy, in tumor-bearing mice, of cancer prodrugs consisting of poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) conjugated to doxorubicin (DOX). Our synthesis of polyMPC–DOX conjugates established prodrugs with tunable drug loading, pH sensitive release kinetics, and a maximum tolerated dose in the range of 30–50 mg/kg (DOX equivalent) in healthy mice. Here we show prolonged circulation of polyMPC–DOX, with a measured in vivo half-life (t1/2) 8 times greater than that of the free drug. We observed reduced drug uptake in healthy tissue, and 2–3 times enhanced drug accumulation in tumors for polyMPC–DOX prodrugs compared to free DOX, using BALB/c mice bearing 4T1 tumors. Prolonged survival and reduced tumor growth were observed in mice receiving the polyMPC–DOX prodrug treatment. Moreover, we evaluated immunogenicity of polyMPC–DOX prodrugs by examining complete blood count (CBC) and characteristic cytokine responses, demonstrating no apparent innate or adaptive immune system response. |
| Databáze: | OpenAIRE |
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