Polymer-Coated Hydroxyapatite Nanoparticles for the Delivery of Statins

Abstract

Statin drugs have been previously reported to increase the activity of osteoblasts, and are being investigated to treat low bone density pathologies. A controlled release nanoparticle drug delivery system may be used to prolong the exposure of osteoblasts to statin. Furthermore, nano-hydroxyapatite (nHA) has known osteoconductive and osteoinductive properties. The success of nanoparticle drug delivery systems is associated with safety, stability, biodegradability, and pharmacological parameters. nHA have been used as gene and drug delivery vehicles, however in vivo studies have shown that nHA aggregate, accumulate in the lungs, and impede the function of pulmonary surfactant. To address some of these challenges, we present a nHA coated with the biodegradable co-polymer poly(glycolide)- poly(ethylene glycol) (PGA-PEG). PGA coating thickness could be precisely tuned by surface initiated ring opening polymerization to control the release of lovastatin. PGA-PEG coated nHA were shown to be internalized in human osteoblasts, and were also shown to maintain 70% cell viability in human umbilical vein endothelial cells at doses up to 500 μg mL-1 in vitro. Preliminary in vivo maximum tolerated dose studies showed that PGA-PEG coated nHA were less toxic compared to uncoated nHA. This hybrid polymer-HA nanoparticle drug delivery system has potential as a controlled release system for the delivery of statins to treat low bone density pathologies.