SLOW-RELEASE OF TETRACYCLINE HYDROCHLORIDE FROM A CELLULOSE MEMBRANE USED IN GUIDED TISSUE REGENERATION

THE OBJECTIVE OF THIS STUDY was to evaluate if the biologic membrane u tilized for GTR can be impregnated by tetracycline hydrochloride and i f the chemotherapeutic agent, once impregnated, can be released in min imal. inhibitory concentrations for a period compatible with clinical application. Initially, an in vitro study was done with cellulose memb ranes cut in pieces measuring 9 cm(2). A volume of 100 mu l containing a 72,000 mu g/ml solution of tetracycline was dispensed onto each fra gment, and dried for 70 minutes at 37 degrees C. Four pieces measuring 0.5 cm(2) were cut from different points of the 9 cm(2) membrane (pre sumably, containing 400 mu g of tetracycline), placed in test tubes co ntaining 4 ml of sterile deionized water, and agitated for 2 minutes. A standard curve was made from known concentrations of tetracycline an d compared to 10 mu l of the test solutions obtained by the elution of the 0.5 cm(2) fragments. The concentrations were determined through t he bioassay technique in 3 duplicate experiments. The samples recovere d from the membrane fragments had a mean of 101 mu g/ml of tetracyclin e liberated, demonstrating that the membrane was impregnated homogeneo usly by the chemotherapeutic agent. In a second phase, an in vivo stud y was carried out to determine the length of time the drug was liberat ed from the membranes and at which concentrations, in the presence of an inflammatory process. Fourteen 0.5 cm(2) fragments containing 400 m u g of tetracycline were placed in 14 polypropylene chambers containin g 200 mu l of thioglycolate medium. The chambers were implanted in the peritoneal cavities of 14 mice, one chamber per animal, and left in f rom 1 to 14 days. They were then removed and the concentrations of tet racycline determined from 20 mu l samples using a bioassay. The result s showed that the antibiotic was released slowly from the Ist through the 12th day in decreasing concentrations that varied from 218 to 20.8 mu g/ml. The impregnated cellulose membrane can probably be used in G TR acting as a membrane and as a slow-release device, liberating the c hemotherapeutic agent in concentrations high enough to eliminate perio dontopathic microorganisms.