Bisphosphonate-Derivatized Liposomes to Control Drug Release from Collagen/Hydroxyapatite Scaffolds

A drug delivery system was developed by combining composite scaffolds made up of collagen and hydroxyapatite (Col/HA) with bisphosphonate (BP)-derivatized liposomes. The Col/HA scaffold was prepared by a freeze-drying method to yield a porous scaffold. The liposomes were composed of distearoylphosphocholine, cholesterol, distearoylphosphoethanolamine-poly(ethylene glycol) (DSPE-PEG), and a bone-binding bisphosphonate (BP) attached to the DSPE-PEG (DSPE-PEG-BP). By taking advantage of the specific interaction between the liposomal BP and the HA incorporated into the scaffold, the BP-decorated liposomes (BP-liposomes) were shown to display a strong affinity to Col/HA scaffolds. Three different model drugs, carboxyfluorescein (CF), doxorubicin (DOX), and lysozyme (LYZ) were entrapped in liposomes; there were no differences in drug release from the liposomes whether the liposomes were BP decorated or not. Whereas unencapsulated drugs and drugs encapsulated in PEG-liposomes displayed rapid release from the scaffolds, the drugs entrapped in BP-liposomes showed a slower release from the Col/HA scaffolds. We conclude that the proposed system can prolong the in situ residence of model drugs and has the potential to provide a sustained drug release platform in bone regeneration and repair.