HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

HSP32 (HO-1) inhibitor, copoly(styrene-maleic acid)-zinc protoporphyrin IX, a water-soluble micelle as anticancer agent: In vitro and in vivo anticancer effect.

Abstract
We reported previously the antitumor effect of heme oxygenase-1 (HO-1) inhibition by zinc protoporphyrin IX (ZnPP). ZnPP per se is poorly water soluble and thus cannot be used as anticancer chemotherapeutic. Subsequently, we developed water-soluble micelles of ZnPP using styrene-maleic acid copolymer (SMA), which encapsulated ZnPP (SMA-ZnPP). In this report, the in vitro and in vivo therapeutic effects of SMA-ZnPP are described. In vitro experiments using 11 cultured tumor cell lines and six normal cell lines revealed a remarkable cytotoxicity of SMA-ZnPP against various tumor cells; average IC(50) is about 11.1 μM, whereas the IC(50) to various normal cells is significantly higher, that is, more than 50 μM. In the pharmacokinetic study, we found that SMA-ZnPP predominantly accumulated in the liver tissue after i.v. injection, suggesting its applicability for liver cancer. As expected, a remarkable antitumor effect was achieved in the VX-2 tumor model in the liver of rabbit that is known as one the most difficult tumor models to cure. Antitumor effect was also observed in murine tumor xenograft, that is, B16 melanoma and Meth A fibrosarcoma. Meanwhile, no apparent side effects were found even at the dose of ∼7 times higher concentration of therapeutics dose. These findings suggest a potential of SMA-ZnPP as a tool for anticancer therapy toward clinical development, whereas further investigations are warranted.
AuthorsJun Fang, Khaled Greish, Haibo Qin, Long Liao, Hideaki Nakamura, Motohiro Takeya, Hiroshi Maeda
JournalEuropean journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 81 Issue 3 Pg. 540-7 (Aug 2012) ISSN: 1873-3441 [Electronic] Netherlands
PMID22576132 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Maleates
  • Metalloporphyrins
  • Micelles
  • Polystyrenes
  • copoly(styrene-maleic acid)-zinc protoporphyrin
  • Heme Oxygenase-1
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage, pharmacology, toxicity)
  • Cell Line
  • Cell Line, Tumor
  • Chick Embryo
  • Chlorocebus aethiops
  • Female
  • Heme Oxygenase-1 (antagonists & inhibitors)
  • Humans
  • Inhibitory Concentration 50
  • Injections, Intravenous
  • Liver (metabolism)
  • Male
  • Maleates (administration & dosage, pharmacology, toxicity)
  • Metalloporphyrins (administration & dosage, pharmacology, toxicity)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Micelles
  • Neoplasms (drug therapy, pathology)
  • Polystyrenes (administration & dosage, pharmacology, toxicity)
  • Rabbits
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: