Payload drug vs. nanocarrier biodegradation by myeloperoxidase- and peroxynitrite-mediated oxidations: pharmacokinetic implications

Details

• Personal Author:
  Kagan VE ; Kapralov AA ; Seo W ; Shurin GV ; Shurin MR ; Star A
• Description:
  With the advancement of nanocarriers for drug delivery into biomedical practice, assessments of drug susceptibility to oxidative degradation by enzymatic mechanisms of inflammatory cells become important. Here, we investigate oxidative degradation of a carbon nanotube-based drug carrier loaded with Doxorubicin. We employed myeloperoxidase-catalysed and peroxynitrite-mediated oxidative conditions to mimic the respiratory burst of neutrophils and macrophages, respectively. In addition, we revealed that the cytostatic and cytotoxic effects of free Doxorubicin, but not nanotube-carried drug, on melanoma and lung carcinoma cell lines were abolished in the presence of tumor-activated myeloid regulatory cells that create unique myeloperoxidase- and peroxynitrite-induced oxidative conditions. Both ex vivo and in vitro studies demonstrate that the nanocarrier protects the drug against oxidative biodegradation. [Description provided by NIOSH]
• Subjects:
  Biopharmaceutics Drug Therapy Occupational Health Oxidants Safety
• Keywords:
  Carbon Nanotubes Drug Therapy Nanotechnology Oxidative Processes Pharmaceuticals Pharmacology
• ISSN:
  2040-3364
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  7
• Issue:
  19
• NIOSHTIC Number:
  nn:20047597
• Citation:
  Nanoscale 2015 May; 7(19):8689-8694
• Contact Point Address:
  Alexander Star, Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
• Email:
  astar@pitt.edu
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Nanoscale
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f3f01656a30b8d59c8bd8ba133a6c14a8c56e55abe4689569a9d5886c67023aacc825bc7b3514d5bba24bfb1b7143c7a8433e375c683950037db91c3419abd3f
• Download URL:
  https://stacks.cdc.gov/view/cdc/202612/cdc_202612_DS1.pdf
• File Type:
  [PDF - 263.62 KB ]