Hydroxyapatite beads containing Doxorubicin hydrochloride (dox) and buthionine sulfoximine (bso) - a new anticancer drug design for local treatment with multiple-drugs.

Doxorubicin hydrochloride (DOX) and buthionine sulfoximine (BSO) were adsorbed on to a drug-carrier, hydroxyapatite (HAP), to form a DOX and BSO-HAP complex. The time-course of the release of these drugs from the complex into phosphate-buffered saline (PBS) was measured photometrically at 37-degrees-C in vitro. After 3 h of incubation, almost all the BSO in the DOX and BSO-HAP complex was released into the PBS, whereas 48.7% of the DOX was released during this period. DOX was released continuously over 10 h of incubation, the rate of release being 7.3%h of the total amount released. Both DOX and BSO were eluted from the DOX and BSO-HAP complex over the first 3 h of incubation. From the 4 h of incubation, only DOX was released, indicating a slow-release property of the complex. The DOX and BSO-HAP complex developed in this study may in future have an in vivo application. It is possible that intracellular glutathione could be depleted first by the rapidly released BSO and that DNA strand breaks could then be intensified by the slowly released DOX. Therefore, this complex has potential as a new drug delivery system (DDS) in cancer chemotherapy.