Superior Penetration and Cytotoxicity of HPMA Copolymer Conjugates of Pirarubicin in Tumor Cell Spheroid
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- Klíčová slova
- HPMA polymer, drug delivery, penetration, pirarubicin (THP), tumor spheroid cell,
- MeSH
- akrylamidy chemie MeSH
- antitumorózní látky aplikace a dávkování farmakokinetika MeSH
- buněčné sféroidy MeSH
- doxorubicin aplikace a dávkování analogy a deriváty farmakokinetika MeSH
- HCT116 buňky MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- nádory farmakoterapie patologie MeSH
- nosiče léků chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akrylamidy MeSH
- antitumorózní látky MeSH
- doxorubicin MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
- nosiče léků MeSH
- pirarubicin MeSH Prohlížeč
N-(2-Hydroxypropyl)methacrylamide copolymer conjugates of pirarubicin (THP), P-THP, accumulates selectively in solid tumor tissue by the enhanced permeability and retention (EPR) effect. Despite of high accumulation in solid tumors, some macromolecular antitumor agents show poor therapeutic outcome because of poor tissue diffusion into the tumor as well as obstructed tumor blood flow. Here, we confirmed that cellular uptake of P-THP was 25 times less than that of free THP at 1-4 h incubation time in vitro. The passage of P-THP through the confluent tight-monolayer cells junction was 12 times higher than free THP, and P-THP penetrated deeper into the tumor cell spheroid (1.3-1.7-fold) than free THP in 4 h. In addition, P-THP showed cytotoxicity comparable to that of free THP to tumor-cells in spheroid form, despite of 7 times lower cytotoxicity of P-THP to the monolayer cells to that of free THP in vitro. These results indicate that P-THP administration can exhibit deeper diffusion into the tumor cell spheroid than free THP. As a consequence, P-THP exhibits more efficient antitumor activity than free THP in vivo, which is also supported by better pharmacokinetics and tumor accumulation of P-THP than free THP.
BioDynamics Research Foundation Kuwamizu 1 24 6 Chuo ku Kumamoto 862 0954 Japan
Department of Microbiology Kumamoto University School of Medical Sciences Kumamoto Japan
Faculty of Pharmaceutical Sciences Sojo University Ikeda 4 22 1 Nishi ku Kumamoto 860 0082 Japan
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