Strontium ranelate-loaded PLGA porous microspheres enhancing the osteogenesis of MC3T3-E1 cells

Abstract

Biodegradable poly lactic-co-glycolic acid (PLGA) has been used as a tissue engineering scaffold as well as a carrier for the delivery of proteins, drugs, and other macromolecules. Hydroxyapatite (HA) nanoparticle self-assembly on the surface of a PLGA microsphere can create a hydrophilic environment, and its hydroxide can neutralize the acidity of PLGA degradation products. These microspheres can be used to deliver strontium ranelate (SR), which is used to treat osteoporosis. In the present study, we fabricated porous PLGA microspheres (PM), SR-loaded (SR-)PM, and SR-PM with HA nanosuspension and polyvinyl alcohol (PVA) as a surfactant (SR-PM-HA) in a S/O/Ns method. The microspheres exhibited an interconnected porous structure. The percent cumulative release of SR from SR-PM was 90% in 22 days as compared to 85% from SR-PM-HA. In both cases, drug release was gradual (with no burst release). SR-PM and SR-PM-HA similarly stimulated the proliferation of MC3T3-E1 cells to a greater degree than PM and induced osteogenic differentiation, as determined by alkaline phosphatase staining and real-time PCR analysis of osteogenic marker gene expression. These results indicate that SR-PM-HA is biocompatible and suitable for drug delivery and osteoinduction.