title: [Effects of Xenobiotics on Drug Pharmacokinetics and Safety].
abstract: The use of nanotechnology has increased over the past 10 years, and various nanomaterials with a wide range of applications have been developed. Carbon nanotubes (CNTs), which are cylindrical molecules consisting of hexagonally arranged carbon atoms, are nanomaterials with high utility. Recently, applications of single-walled CNT (SWCNT) in the medical field for drug-delivery and as gene-delivery agents have been proposed. Due to its structural characteristics and physicochemical properties, the inhalation of SWCNT could be considered as one route for targeted drug delivery into the lungs. Therefore, it is necessary to investigate the effects of SWCNT on the physiological state and response of the cells upon delivery into the lung. We clarified the different response of two carcinoma cell lines to SWCNT exposure, and determined these differences may be due to different cell functions. Furthermore, SWCNT exposure resulted in a global downregulation of stress-responsive genes in normal human bronchial epithelial cells, thereby indicating that the factors involved in the stress responses were not activated by SWCNT. We then tried to ascertain the possible effect of SWCNT on the fate of drugs delivered with SWCNT. Exposure to SWCNT down-regulated the mRNA expression and enzymatic activity of CYP1A1 and CYP1B1 by preventing the binding of activated aryl hydrocarbon receptors to the enhancer region of these genes. This review provides basic information for the prediction of human responses to SWCNT exposure by inhalation, and in its use as a drug delivery carrier.
authors.affiliation: Faculty of Pharmacy, Meijo University.
authors.forename: Miki
authors.initials: M
authors.lastname: Katoh
mesh_terms: D000280:Administration, Inhalation; D001980:Bronchi / Q000166:cytology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D016503:Drug Delivery Systems; D004742:Enhancer Elements, Genetic; D004847:Epithelial Cells; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D006801:Humans; D008168:Lung / Q000378:metabolism; D037742:Nanotubes, Carbon; D010599:Pharmacokinetics; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D012449:Safety; D013312:Stress, Physiological / Q000235:genetics; D015262:Xenobiotics / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*
chemical_list: D037742:Nanotubes, Carbon; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1