An in vivo study on the reaction of hydroxyapatite-sol injected into blood

J Mater Sci Mater Med. 2000 Feb;11(2):67-72. doi: 10.1023/a:1008993814033.


In order to identify the possibility of hydroxyapatite-sol being used as a drug carrier and absorbent, an in vivo experimental study was performed. Pure hydroxyapatite microcrystals were synthesized by reaction of high purity Ca(OH)2 and H3PO4 solutions while using an ultrasonic homogenizer. Hydroxyapatite-sol was prepared by dispersing hydroxyapatite microcrystals into physiological salt solution. The hydroxyapatite-sol in different concentrations was injected into veins of both 25 Wistar rats and 5 Beagle dogs. The medium lethal dose was determined as 160 mg/kg. By observing the change of O2 and CO2 gas partial pressure, it was considered that the main cause of death by hydroxyapatite-sol injection was due to the blockage of capillaries. When one-sixth amount of the medium lethal dose was injected into the veins of the dogs, the value of phosphorous increased but calcium and magnesium kept stable. LDH, CPK, GOP and GDT values dramatically increased in 30 min after injection, however, one day after injection, the values returned to normal. Repeated experiments by similar methods were continued on same animals for 2 years in two-week intervals, the results in every experiment were almost same, no chronic damage or permanent side effects were discovered in the two years experiment. According to the results above, it was suggested that the hydroxyapatite-sol could be applied as a drug carrier into blood by using a small amount less than one-sixth of the medium lethal dose.