ИСТИНА

The basic challenge of the pre-clinical trials of nanodiamonds-mediated drug delivery systems is the study on ND accumulation and excretion in vivo. First of all, it is necessary at studies on pharmacokinetics, the mode of introduction and development of optimal dosage form. So far, this question is considered by several studies and remains largely unknown [1-4]. The focus of the present work was to study ex vivo biodistribution of iodine labeled nanodiamond particles in rabbits (n = 5) during the month by inductively coupled plasma mass spectrometry (ICP-MS). The ICP-MS technic was as follows. Previously nanodiamonds were annealed in a stream of hydrogen gas and chlorinated with photochemical initiation of molecular chlorine. Then nanodiamonds were functionalized with iodine-containing compound – (2,4,6-triiodophenyl)methanol. Rabbits were treated once with this conjugate by intravenous injection in dosage 5 mg/kg. Organs were excised and homogenized 1, 6, 24 h, 15 and 30 days after administration. The resulting mixture was subjected to the sample preparation, which includes ultrasonic processing samples immediately before the measurement. Further a direct measurement of the iodine accumulated in separate organs was performed using mass spectrometer Perkin Elmer DRC-2, detecting the isotope content 127I. The detection limit of isotope 127I is 0.008 mg/l. There were analyzed six main types of organ: lung, kidney, spleen, liver, heart and cerebrum. Device calibration for the measurement was performed using standard samples prepared by SSS 7956-2001 dilution in 1% solution of NaOH to concentrations of 10, 5, 1, 0.5, 0.1, 0.05 and 0.01 mg/ml, respectively. These studies have revealed sufficiently fast and maximal nanodiamonds cumulation in lungs (up to 30 μg/kg) and spleen (up to 23 μg/kg) of rabbits. Limiting nanodiamonds content in other organs attained slowly: the liver and the brain - through the one day, and in the kidneys and heart - on the 15th day. Nanodiamonds were accumulated in the heart and brain of animal in quantity of 6.5 μg/g and excreted almost all bodies during one month. The resulting data allow to study in details nanodiamonds biodistribution and pharmacokinetics in vivo by development and application of nanodiamonds-mediated drug delivery systems. This work was supported by RFBR (grant 11-03-00543).