Development of ceramic nanocarrier based delivery systems with desired controlled drug release profiles seems to be an efficient way for the treatment of many bacterial infections such as periodontitis. Nanocrystalline calcium-deficient hydroxyapatites (CDHA) are of greater biological interests due to the similarity in size and composition with the mineral component of hard tissues. Doxycycline is a broad-spectrum antibiotic widely utilized for the treatment of juvenile periodontitis. In the present study, the drug release kinetics of doxycycline-loaded nanocarriers of CDHA ceramics has been evaluated for the first time. The CDHAs with different calcium/phosphorus ratio were also studied to evaluate the effect of the composition on the release profiles. The ceramic nanocarriers were synthesized using microwaves and were well characterized by X-ray powder diffraction, infrared spectroscopy, and electron microscopic techniques. The amount of doxycycline uptake by CDHA with varying pH showed a maximum amount at the physiological pH of 7.4. The nanocarriers exhibit both single and two stage release profiles of doxycycline depending on the Ca/P ratio of CDHA. The initial bursting release is due to desorption of doxycycline from the CDHA surface, followed by a slow release as a result of the dissolution of the doxycycline-CDHA complex nanocarriers. The duration of drug release was remarkably longer from 3 to 5 days for nanocarriers with Ca/P ratios similar to bone which are typically required for effective antibiotic therapy. CDHA nanocarriers may thus be useful for sustained release of doxycycline for the treatment of bacterial bone infections. Copyright © 2008 American Scientific Publishers All rights reserved.