title: Liposomal encapsulation masks genotoxicity of a chemotherapeutic agent in regulatory toxicology assessments.
abstract: The burgeoning application of nanotechnology to a variety of industries including cosmetics, food, medicine and materials has led to the exploration of nanotoxicology as a trending subject of research. However the role of a nanovector, in affecting the mutagenicity of its therapeutic payload has not yet been investigated. In this study, we compare the mutagenicity of the free drug - doxorubicin hydrochloride with its nanoencapsulated form - doxorubicin loaded liposome, using conventional methods required for regulatory approval. Contrary to free doxorubicin, doxorubicin encapsulated liposome expressed a significantly lower mutant frequency in the Ames assay, and was non-genotoxic in the in vitro micronucleus assay. Further investigation of the systems' cytotoxicity and their interaction with the bacterial cell envelope, suggests that the modification of the test parameters and release of the encapsulated drug prior to the Ames test show comparable mutagenic potential of the nanotherapeutic system to a free drug.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX.
authors.forename: Jenolyn F
authors.initials: JF
authors.lastname: Alexander
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX.
authors.forename: David
authors.initials: D
authors.lastname: Aguirre-Villarreal
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX. Electronic address: bianagodinv@gmail.com.
authors.forename: Biana
authors.initials: B
authors.lastname: Godin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity*; D016466:CHO Cells; D003412:Cricetulus; D004317:Doxorubicin / Q000008:administration & dosage* / Q000633:toxicity*; D008081:Liposomes; D050296:Microbial Viability / Q000187:drug effects; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests / Q000379:methods*; D012486:Salmonella typhimurium / Q000166:cytology / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D004317:Doxorubicin
keywords: Ames assay; Genotoxicity; Liposome; Mutagenicity; Nano; Toxicity