Peroxotitanates for biodelivery of metals

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 (SDH‐MTT 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. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009