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

Yuya Hirano; Yasuhiko Iwasaki

doi:10.1016/j.colsurfb.2017.02.015

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

Colloids Surf B Biointerfaces. 2017 May 1:153:104-110. doi: 10.1016/j.colsurfb.2017.02.015. Epub 2017 Feb 16.

Authors

Yuya Hirano¹, Yasuhiko Iwasaki²

Affiliations

¹ Graduate School of Science and Engineering, Kansai University, 3-3-35 Yamate-cho, Suita-shi, Osaka, 564-8680, Japan.
² Department of Chemistry and Materials, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35 Yamate-cho, Suita-shi, Osaka, 564-8680, Japan; ORDIST, Kansai University, 3-3-35 Yamate-cho, Suita-shi, Osaka, 564-0836, Japan. Electronic address: yasu.bmt@kansai-u.ac.jp.

PMID: 28231498
DOI: 10.1016/j.colsurfb.2017.02.015

Abstract

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.

Keywords: Biodegradable polymer; Bone therapy; Drug delivery system; Nanoparticle; Polyphosphoester; Ring-opening polymerization.

MeSH terms

Adsorption
Animals
Biocompatible Materials / chemical synthesis
Biocompatible Materials / chemistry
Biocompatible Materials / metabolism*
Bone Resorption / metabolism*
Cattle
Cell Line
Cell Survival
Materials Testing
Mice
Nanoparticles / chemistry
Nanoparticles / metabolism*
Osteoclasts
Particle Size
Polyethylenes / chemical synthesis
Polyethylenes / chemistry
Polyethylenes / metabolism*
Surface Properties

Substances

Biocompatible Materials
Polyethylenes
poly(ethylene sodium phosphate)