Injectable self-curing bioactive acrylic-glass composites charged with specific anti-inflammatory/analgesic agent

Abstract

Injectable bioactive acrylic formulations based on poly(methyl methacrylate) (PMMA) and different amounts of bioactive glasses in the system SiO 2–CaO–Na 2O–P 2O 5 have been prepared in the presence of the anti-inflammatory analgesic drug fosfosal, the sodium salt of 2-phosphonoxibenzoic acid, to be used in minimally invasive surgery. The injectability of the formulations evaluated according to the established protocol was around 80%. The experimental formulations provided maximum temperatures in the range 50–60°C, which were lower than those of commercial acrylic bone cements currently used in percutaneous vertebroplasty (PVP). Residual monomer content of any formulation was inferior to 5%. Compressive yield strength of dry specimens was in the range 80–95 MPa, but it decreased after immersion in SBF to values in the range 30–50 MPa, due to the dissolution of the bioactive glasses and the drug in the medium. The release of fosfosal was evaluated in vitro (pH=7.0). The release profile against time obtained from a PMMA cement was quasi-linear and the 80% of the initial amount of drug was released in 175 h. However, for bioactive cements, the 80–100% of the fosfosal charged was released in approximately 48 h, due to the dissolution of the glasses in the medium. Values of weight loss of the cements determined gravimetrically ranged between 16% and 26% depending on the initial amount of fosfosal, i.e. 20 or 30 wt%, respectively. The weight loss and the water uptake were simultaneous processes, and values of hydration degree were around 10–14%. The formation of an apatite-like layer was detected on the surface of the cements at different periods of time depending on the composition of the bioactive glasses. The cements containing the glasses with P 2O 5 produced the growth of the apatite layer in shorter periods of time. The presence of fosfosal accelerated the precipitation of this layer independently on the glasses. The in vivo biocompatibility studied by intramuscular implantation in rats showed the absence of an anti-inflammatory response and a fibrous layer around the implant for the cement prepared with PMMA/fosfosal which is attributed to the therapeutic action of fosfosal acting in situ. The response to cements prepared with bioactive glasses and fosfosal showed a mild inflammatory reaction with the formation of the typical fibrous capsule around the implanted material.