Hybrid injectable platforms for the in situ delivery of therapeutic ions from mesoporous glasses

Abstract

Copper-containing bioactive glasses (Cu-MBGs) are attracting increasing interest as multifunctional agents for hard and soft tissue healing due to the ability of released copper ions to stimulate osteogenesis as well as angiogenesis and to impart anti-bacterial properties. The conjugation of these nanomaterials with a vehicle phase based on thermosensitive hydrogels represents an effective strategy to design non-invasive injectable devices for the in situ delivery of therapeutic ions from MBGs.In this contribution, Cu-containing MBGs were prepared by an aerosol-assisted spray-drying method (MBG_Cu 2%_SD) in the form of microspheres (surface area of ca 220 m2 g−1) and through a sol-gel synthesis (MBG_Cu 2%_SG) in the form of spheroidal nanoparticles (surface area above 700 m2 g−1). Both Cu-containing samples were able to release copper ions, although with different rates and percentage release. MBG_Cu 2%_SG released the total incorporated amount of Cu ions with a faster kinetics compared to MBG_Cu 2%_SD, that released approximately the 60% of copper.Cu-MBGs were incorporated with a final concentration of 20 mg/mL into a thermosensitive sol-gel system consisting of a novel amphiphilic poly(ether urethane) based on a commercialy available Poloxamer 407 (P407), with improved gelation ability, mechanical strength and stability in aqueous solution with respect to native P407. Cu-MBG-loaded hydrogels were characterised in terms of sol-to-gel transition temperature and time, injectability and stability in aqueous environment at 37 °C. The hybrid formulations showed fast gelation in physiological conditions (1 mL underwent complete sol-to-gel transition within 3–5 min at 37 °C) and injectability in a wide range of temperatures (5–37 °C) through different needles (inner diameter in the range 0.6–1.6 mm).When embedded into the hydrogel, Cu-MBGs retained their release properties, showing a sustained delivery of Cu2+ along 14 days.