Study of implantable calcium phosphate systems for the slow release of methotrexate

The authors prepared and studied systems implantable in bone, for the slow release of an antineoplasic agent, methotrexate (MTX). The systems were made by compaction of a powdered mixture of an apatitic deficient calcium phosphate, dextran and various amounts of MTX. Used as a matrix, this calcium phosphate has outstanding adsorption and compaction properties. It is an osteoconductor and biodegradable. The in vitro study carried out on these systems showed that the release of MTX with time is slow and prolonged due to the phenomena of adsorption/desorption of MTX onto deficient apatite. The composition of the implants changed with time towards that of stoichiometric apatite. The in vivo pilot study was performed by implantation in the external femoral condyle of rabbits. A pharmacokinetic study revealed that the circulating concentration of MTX in the blood was always below toxic levels. Twenty percent of the initial MTX remained in the implants after 7 days. A study of the biocompatibility and bioreactivity showed no local necrosis at any time, while implants degraded and new bone formed simultaneously. These implantable systems seem appear suitable for use immediately.