Tris trimethylsilyl phosphite

Hybrid organo–inorganic sol–gel coatings composed by a mixture of organopolysyloxanes: methacryloxypropyltrimethoxy silane (MAPTMS, 98%, Acros Organics, Thermo Fisher Scientific, Waltham, MA, USA) and tetramethyl orthosilane (TMOS, 98%, Acros Organics, Thermo Fisher Scientific, Waltham, MA, USA) and biofunctionalized with tris(tri-methylsilyl)phosphite (92%, Sigma–Aldrich, St. Louis, MO, USA) were prepared following a previously published methodology [24 (link)]. Three coatings were loaded with the following quantities of fluconazole (Sigma-Aldrich, St. Louis, MO, USA): 0.65 (F50), 0.975 (F75), and 1.3 (F100) mg/mL sol–gel; alternatively, they were loaded with anidulafungin (Pfizer, New York, NY, USA) in the following quantities: 0.49 (A50), 0.74 (A75), and 0.99 (A100) mg/mL sol–gel. Functionalization of the coatings with antifungal drugs was performed by adding the drug to the aqueous phase during its preparation. These concentrations have been intentionally chosen because they represent 50%, 75% and maximum amount of this antifungal which sol–gel can contain without compromising its stability, durability, and adherence on titanium (Ti) substrates. Sol–gel functionalized with organophosphite without the addition of antifungals was used as a control (P2).

The Ti-6Al-4V implants were made from 0.6-mm thick Kirschner wires provided by Depuy Synthes (Johnson & Johnson, New Brunswick, NJ, USA). Each wire was cut into implants measuring 1 cm in length. Subsequently, these were chemically polished (CP), as previously described [44 (link)], to achieve a surface finish more closely resembling that used in routine clinical practice.
Hybrid organic–inorganic sol-gel coatings composed of a mixture of organopolysyloxanes, including methacryloxypropyltrimethoxy silane (MAPTMS, 98%, Acros Organics, Thermo Fisher Scientific, Waltham, MA, USA) and tetramethyl orthosilane (TMOS, 98%, Acros Organics, Thermo Fisher Scientific, Waltham, MA, USA) and biofunctionalised with tris(trimethylsilyl)phosphite (92%, Sigma-Aldrich, St. Louis, MO, USA) were prepared following a previously published methodology [23 (link)]. The coating was loaded with 0.99 mg/mL of anidulafungin (Pfizer, New York, NY, USA) by adding the drug to the aqueous phase during its preparation [22 (link)]. Finally, the Ti-6Al-4V implants for the in vivo model were coated by dipping them in anidulafungin and allowing them to dry for at least 1 h at 60 °C (CP + A).