Bone-specific poly(ethylene sodium phosphate)-bearing biodegradable nanoparticles

Chemotherapy is the most reliable treatment for osteoporosis and osseous metastases. To facilitate better drug delivery for bone treatments, a novel preparation of polymeric nanoparticles with high affinity to bone has been prepared. Two-step synthesis of cholesteryl-functionalized poly(ethylene sodium phosphate) (Ch-PEP_n·Na) was performed via ring-opening polymerization of cyclic phosphoesters and the demethylation. The molecular weight of Ch-PEP_n·Na could be well controlled by changing the ratio of cholesterol and cyclic phosphoesters. Because Ch-PEP_n·Na exhibits an amphiphilic nature in aqueous media, Ch-PEP_n·Na-bearing nanoparticles (PEP_n·Na NPs) were prepared by a solvent evaporation technique. The size of the nanoparticles investigated in the current study is approximately 100nm, which was determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Due to the presence of highly water-soluble polymer chains, dispersion of PEP_n·Na NPs in aqueous media was stable for at least 1 week. Hemolytic activity of PEP_n·Na NPs was found to be low and PEP_n·Na NPs did not disintegrate mammalian cell membranes. Additionally, cytotoxicity of PEP_n·Na NPs was not observed at concentrations below 100μg/mL. The adsorption of PEP_n·Na NPs on hydroxyapatite (HAp) microparticles was studied in comparison with poly(ethylene glycol) nanoparticles (PEG NPs). Both PEP_n·Na NPs and PEG NPs adsorbed well onto HAp microparticles in distilled water with binding equilibrium constants (K_HAp) for PEP_n·Na NPs and PEG NPs of 3.6×10⁶ and 7.9×10⁶, respectively. In contrast, only PEP_n·Na NPs adsorbed onto HAp microparticles in a saline phosphate buffer. Moreover, the adsorption of PEP_n·Na NPs onto HAp microparticles occurred even in the presence of 1.2mM calcium ions or low-pH media. The affinity of the nanoparticles to bovine bone slices was also studied, with the result that large quantities of adsorbed PEP_n·Na NPs were observed on the slices by scanning electron microscope.