Bone targeting potential of bisphosphonate-targeted liposomes. Preparation, characterization and hydroxyapatite binding in vitro.

The main constituent of bone is hydroxyapatite (HAP). Since HAP is only present in 'hard' tissues like bone and teeth, it represents a promising target for the selective drug delivery to bone. Due to the exceptional affinity of bisphosphonates (BP) for HAP, cholesteryl-trisoxyethylene-bisphosphonic acid (CHOL-TOE-BP), a new tailor-made BP derivative, was used as bone targeting moiety for liposomes. CHOL-TOE-BP-targeted liposomes were designed for the treatment of bone-related diseases to achieve prolonged local exposure to high concentrations of the bioactive compounds, thereby enhancing therapeutic efficacy and minimizing systemic side effects. The CHOL-TOE-BP-targeted liposomes were characterized regarding particle size and zeta potential. To study the bone targeting potential of these conjugates, an in vitro HAP binding assay was established. The obtained binding data indicate that CHOL-TOE-BP is useful as targeting device for liposomal drug delivery to bone.