title: Atomic force microscopy images label-free, drug encapsulated nanoparticles in vivo and detects difference in tissue mechanical properties of treated and untreated: a tip for nanotoxicology.
abstract: Overcoming the intractable challenge of imaging of label-free, drug encapsulated nanoparticles in tissues in vivo would directly address associated regulatory concerns over 'nanotoxicology'. Here we demonstrate the utility of Atomic Force Microscopy (AFM) for visualising label-free, drug encapsulated polyester particles of ∼280 nm distributed within tissues following their intravenous or peroral administration to rodents. A surprising phenomenon, in which the tissues' mechanical stiffness was directly measured (also by AFM) and related to the number of embedded nanoparticles, was utilised to generate quantitative data sets for nanoparticles localisation. By coupling the normal determination of a drug's pharmacokinetics/pharmacodynamics with post-sacrifice measurement of nanoparticle localisation and number, we present for the first time an experimental design in which a single in vivo study relates the PK/PD of a nanomedicine to its toxicokinetics.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Lamprou
authors.forename: Vinod
authors.initials: V
authors.lastname: Venkatpurwar
authors.forename: M N V Ravi
authors.initials: MN
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004339:Drug Compounding; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018625:Microscopy, Atomic Force; D050997:Nanomedicine; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D009928:Organ Specificity / Q000187:drug effects*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D014116:Toxicology
chemical_list: D016572:Cyclosporine