title: Peroxotitanates for biodelivery of metals.
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 (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.
authors.affiliation: Department of Restorative Dentistry, University of Washington, Seattle, Washington 98026.
authors.forename: John C
authors.initials: JC
authors.lastname: Wataha
authors.affiliation: Savannah River National Laboratory, Aiken, South Carolina 29801.
authors.forename: David T
authors.initials: DT
authors.lastname: Hobbs
authors.affiliation: Department of Oral Biology, Medical College of Georgia School of Dentistry, Augusta, Georgia 30912.
authors.forename: Petra E
authors.initials: PE
authors.lastname: Lockwood
authors.affiliation: Department of Oral Biology, Medical College of Georgia School of Dentistry, Augusta, Georgia 30912.
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Davis
authors.affiliation: Savannah River National Laboratory, Aiken, South Carolina 29801.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Elvington
authors.affiliation: Department of Oral Biology, Medical College of Georgia School of Dentistry, Augusta, Georgia 30912.
authors.forename: Jill B
authors.initials: JB
authors.lastname: Lewis
authors.affiliation: Department of Oral Biology, Medical College of Georgia School of Dentistry, Augusta, Georgia 30912.
authors.forename: Regina L W
authors.initials: RLW
authors.lastname: Messer
mesh_terms: D002460:Cell Line; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008670:Metals / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D019216:Metals, Heavy / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects; D010087:Oxides / Q000737:chemistry*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D014025:Titanium / Q000737:chemistry*
chemical_list: D004396:Coloring Agents; D004337:Drug Carriers; D008670:Metals; D019216:Metals, Heavy; D010087:Oxides; D013778:Tetrazolium Salts; D013844:Thiazoles; D014025:Titanium; D013385:Succinate Dehydrogenase; C022616:thiazolyl blue
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