title: In vivo biodistribution and clearance of peptide amphiphile micelles.
abstract: Peptide amphiphiles (PAs) are promising biomaterials for medical applications. To translate the use of PAs successfully from laboratories to clinics, in vivo studies regarding the safety of these nanomaterials are required. To examine the toxicity and clearance of PA biomaterials, we intravenously administered cy7-labeled, spherical PA micelles, control micelles without a peptide sequence, or PBS in a murine model and investigated biocompatibility, biodistribution, and clearance. Both peptide and non-peptide labeled micelles were approximately 8 nm in diameter, but of opposite surface charge. Neither micelle type caused aggregation or hemolysis of red blood cells. All micelles primarily accumulated in the bladder and were present in urine samples confirming elimination through renal clearance. Ex vivo imaging showed that micelles were also found in the liver suggesting some involvement of the reticuloendothelial system. However, no evidence of toxicity was found within the liver, spleen, kidney, bladder, intestines, lung, and heart.
  
  
  BACKGROUND
  Safety studies related to peptide amphiphile biomaterials are discussed in this paper, demonstrating that organotoxicity is unlikely with these materials, however, RES activation in the liver may be of consideration in further studies and needed for potential applications.
authors.affiliation: Institute for Molecular Engineering, University of Chicago, Chicago, IL, USA.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Chung
authors.affiliation: Dept. of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA.
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Mlinar
authors.affiliation: Institute for Molecular Engineering, University of Chicago, Chicago, IL, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sugimoto
authors.affiliation: Institute for Molecular Engineering, University of Chicago, Chicago, IL, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Nord
authors.affiliation: Dept. of Radiology, University of Chicago, Chicago, IL, USA.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Roman
authors.affiliation: Institute for Molecular Engineering, University of Chicago, Chicago, IL, USA. Electronic address: mtirrell@uchicago.edu.
authors.forename: Matthew
authors.initials: M
authors.lastname: Tirrell
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects* / Q000627:therapeutic use; D002232:Carbocyanines / Q000008:administration & dosage; D004912:Erythrocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D051379:Mice; D008823:Micelles; D049329:Nanostructures / Q000009:adverse effects* / Q000627:therapeutic use; D010455:Peptides / Q000009:adverse effects* / Q000627:therapeutic use; D014018:Tissue Distribution / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D002232:Carbocyanines; D008823:Micelles; D010455:Peptides; C501744:indotricarbocyanine
keywords: Biodistribution; Clearance; Micelle; Nanoparticle; Peptide amphiphile