title: Longitudinal monitoring of skin accumulation of nanocarriers and biologicals with fiber optic near infrared fluorescence spectroscopy (FONIRS).
abstract: Systemically injected drug delivery systems distribute into various organs and tissues, including liver, spleen and kidneys. Recent reports pointed out a significant accumulation of systemically injected nanoparticles in the skin. Skin constitutes the largest organ in the body with important immune functions, and accumulation of drug delivery systems could have significant implications for skin toxicity in living subjects. Fiber optic-based near-infrared spectroscopy (FONIRS) setup was developed and tested for measuring of NIR (760nm excitation) emission spectra in the skin. Ex vivo spectral measurements of NIR fluorescence through the skin showed linear response down to 34 femtomole of dye DiR. Following systemic injection of IRDye 800 labeled 500kDa dextran, FONIRS detected an immediate and stable accumulation of fluorescence in the skin. Longitudinal monitoring of skin accumulation and elimination of IRDye 800-labeled therapeutic anti-epidermal growth factor antibody (cetuximab) showed significant signal in the skin after the antibody cleared from circulation. Comparison of skin accumulation of DiR labeled, long-circulating PEGylated liposomes with short-circulating non-PEGylated liposomes showed much higher accumulation of PEGylated liposomes that persisted several days after the liposomes cleared from blood. Measurements with FONIRS enabled to estimate skin concentration of liposomes (percent of injected dose per gram). This simple and practical approach can be used to monitor accumulation of drug delivery systems in preclinical and clinical studies.
authors.affiliation: The Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Blvd., Aurora, CO 80045, USA.
authors.forename: James I
authors.initials: JI
authors.lastname: Griffin
authors.affiliation: Sonrgy Inc., 10655 Sorrento Valley Rd., San Diego, CA 92121, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Benchimol
authors.affiliation: The Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Blvd., Aurora, CO 80045, USA. Electronic address: dmitri.simberg@ucdenver.edu.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Simberg
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000493:pharmacokinetics*; D000068818:Cetuximab / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000493:pharmacokinetics*; D004867:Equipment Design; D008081:Liposomes / Q000493:pharmacokinetics*; D008807:Mice, Inbred BALB C; D061848:Optical Imaging / Q000295:instrumentation; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013050:Spectrometry, Fluorescence / Q000295:instrumentation*
chemical_list: D000074322:Antineoplastic Agents, Immunological; D004337:Drug Carriers; D008081:Liposomes; D000068818:Cetuximab
keywords: Antibody; Imaging; Infrared; Liposomes; Skin