title: Evaluation of the toxicity of intravenous delivery of auroshell particles (gold-silica nanoshells).
abstract: Gold nanoshells (155 nm in diameter with a coating of polyethylene glycol 5000) were evaluated for preclinical biocompatibility, toxicity, and biodistribution as part of a program to develop an injectable device for use in the photothermal ablation of tumors. The evaluation started with a complete good laboratory practice (GLP) compliant International Organization for Standardization (ISO)-10993 biocompatibility program, including cytotoxicity, pyrogenicity (US Pharmacopeia [USP] method in the rabbit), genotoxicity (bacterial mutagenicity, chromosomal aberration assay in Chinese hamster ovary cells, and in vivo mouse micronucleus), in vitro hemolysis, intracutaneous reactivity in the rabbit, sensitization (in the guinea pig maximization assay), and USP/ISO acute systemic toxicity in the mouse. There was no indication of toxicity in any of the studies. Subsequently, nanoshells were evaluated in vivo by intravenous (iv) infusion using a trehalose/water solution in a series of studies in mice, Sprague-Dawley rats, and Beagle dogs to assess toxicity for time durations of up to 404 days. Over the course of 14 GLP studies, the gold nanoshells were well tolerated and, when injected iv, no toxicities or bioincompatibilities were identified.
authors.affiliation: Gad Consulting Services, 102 Woodtrail Lane, Cary, NC 27511, USA. scgad@ix.netcom.com
authors.forename: Shayne C
authors.initials: SC
authors.lastname: Gad
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Sharp
authors.forename: Charles
authors.initials: C
authors.lastname: Montgomery
authors.forename: J Donald
authors.initials: JD
authors.lastname: Payne
authors.forename: Glenn P
authors.initials: GP
authors.lastname: Goodrich
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced; D006224:Cricetinae; D004247:DNA / Q000187:drug effects; D004285:Dogs; D005260:Female; D017612:Gold Compounds / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*; D007275:Injections, Intravenous; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D057145:Nanoshells / Q000627:therapeutic use / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010858:Pigmentation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D017612:Gold Compounds; D004247:DNA