Preparation and characterization of polyphosphoester coated nanoparticles having a potential for delivery of hydrophobic drugs to bone

Abstract

Event Abstract Back to Event Preparation and characterization of polyphosphoester coated nanoparticles having a potential for delivery of hydrophobic drugs to bone Yuya Hirano1* and Yasuhiko Iwasaki2, 3* 1 Kansai university, Graduate School of Science and Engineering, Japan 2 Kansai university, Faculty of Chemistry, Materials and Bioengineering, Japan 3 Kansai university, ORDIST, Japan Introduction: Bone is the most common metastatic site of epithelial cancers. Chemotherapy is the currentry most reliable treatment for bone metastasis. To improve the efficacy of the chemotherapy, several nanoparticles (NPs) have been proposed. Particularly, the nanoparticles bering bisphosphonates are usefule to deliver drugs to bone substrates[1]. We have recently proposed poly(ethylene phosphate) as a bone seeking polymer because the polymer shows higher affinity to hydroxyapatite (HAp) compared with bisphosphonates[2]. In the present study, we prepared poly (L-lactic acid) (PLLA) NPs coated with poly(ethylene phosphate) to obtain a drug carrier to specifically deliver chemotherapeutics to bone. Materials and Methods: Cholesteryl-terminated poly(ethylene sodium phosphate) (CH-PEP-Na) was synthesized according to a previously described method[3]. PLLA was dissolved in chloroform and the solution was dropped into the aqueous solution containing CH-PEP-Na at 0oC. The mixture was sonicated using a probe-type sonicator and chloroform was then evaporated under reduced pressure. PLLA NPs coated poly(ethylene glycol) (PEG) were prepared as a control. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to characterize prepared NPs. Cytotoxicity assay using MC3T3-E1 cells and hemolysis test were also carried out. To evaluate affinity of PEP-Na coated NPs to HAp, fluorophore-conjugated NPs were prepared, and contacted with HAp and calculated adsorption constant (KHAp). Results: PEP-Na coated NPs had approximately 100 nm in diameter and spherical shape as shown in Fig.1. NPs prepared by using PEG had similar size and morphology. Cytotoxicity and hemolytic activity of NPs were similar to those of negative control. Fig. 2 shows binding isotherms of NPs on HAp microparticles. KHAp of PEP-Na and PEG coated NPs suspended in PBS(-) calculated using Langmuir equation were 1.42×107 M-1 and 3.29×106 M-1, respectively. Discussion: The NPs coated PEP-Na could have a good dispersibility due to a spherical morphology and negative ζ-potential. The results of cytotoxicity assay using MC3T3-E1 cells and hemolysis test revealed that PEP-Na coated NPs had biocompatibility. The KHAp value of PEP-Na coated NPs in PBS (-) was higher than that of PEG coated NPs in PBS (-) and was similar to that of alendronate (1.6×107 M-1), so it was shown that PEP-Na coated NPs had high HAp-affinity. Conclusion: In the present study, we prepared poly(ethylene phosphate) coated PLLA NPs. Particle size of the NPs was about 100 nm, moreover, we revealed the NPs had excellent biocompatibility and HAp-affinity. The NPs could also encapsulate hydrophobic fluorephore. It is expected from our results that the NPs could incorporate hydrophobic drugs and deliver them to bone.