Peroxotitanates for biodelivery of metals

John C. Wataha, David T. Hobbs, Petra E. Lockwood, Ryan R. Davis, Mark C. Elvington, Jill B. Lewis, Regina L.W. Messer

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Metal-based drugs are largely undeveloped in pharmacology. One limiting factor is the systemic toxicity of metal-based compounds. A solid-phase, sequestratable delivery agent for local delivery of metals could reduce systemic toxicity, facilitating new drug development in this nascent area. Amorphous peroxotitanates (APT) are ion-exchange materials with high affinity for several heavy metal ions and have been proposed to deliver or sequester metal ions in biological contexts. In the current study, we tested a hypothesis that APTs are able to deliver metals or metal compounds to cells. We exposed fibroblasts (L929) or monocytes (THP1) to metal-APT materials for 72 h in vitro and then measured cellular mitochondrial activity (SDHMTT method) to assess the biological impact of the metal-APT materials versus metals or APT alone. APT alone did not significantly affect cellular mitochondrial activity, but all metal-APT materials suppressed the mitochondrial activity of fibroblasts (by 30-65% of controls). The concentration of metal-APT materials required to suppress cellular mitochondrial activity was below that required for metals alone, suggesting that simple extracellular release of the metals from the metal-APT materials was not the primary mechanism of mitochondrial suppression. In contrast to fibroblasts, no metal-APT material had a measurable effect on THP1 monocyte mitochondrial activity, despite potent suppression by metals alone. This latter result suggested that "biodelivery" by metal-APT materials may be cell type-specific. Therefore, it appears that APTs are plausible solid-phase delivery agents of metals or metal compounds to some types of cells for potential therapeutic effect.

Original languageEnglish (US)
Pages (from-to)489-496
Number of pages8
JournalJournal of Biomedical Materials Research - Part B Applied Biomaterials
Volume91
Issue number2
DOIs
StatePublished - Nov 1 2009

Keywords

  • Cytotoxicity
  • Drug delivery
  • Heavy metals
  • Mitochondrial activity
  • Monocyte

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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  • Cite this

    Wataha, J. C., Hobbs, D. T., Lockwood, P. E., Davis, R. R., Elvington, M. C., Lewis, J. B., & Messer, R. L. W. (2009). Peroxotitanates for biodelivery of metals. Journal of Biomedical Materials Research - Part B Applied Biomaterials, 91(2), 489-496. https://doi.org/10.1002/jbm.b.31402