In vitro tobramycin elution analysis from a novel β‐tricalcium phosphate–silicate‐xerogel biodegradable drug‐delivery system

Abstract

This in vitro research analyzed local tobramycin elution characteristics from a novel, biodegradable drug delivery system, consisting of a beta-TCP bone substitute, VITOSS trade mark, encapsulated with silicate xerogel prepared by the sol-gel process. Tobramycin elution from silicate-xerogel-encapsulated VITOSS was compared directly with non-silicate-xerogel-encapsulated VITOSS to assess whether xerogels are effective in delivering greater tobramycin quantities in a controllable, sustained manner crucial for microbial inhibition. Tobramycin elution characteristics indicate an initial release maximum during the first 24 h that diminishes gradually several days after impregnation. The copious tobramycin quantity eluted from the VITOSS/silicate-xerogel systems is attributed to various factors: the intrinsic ultraporosity and hydrophilicity of VITOSS, the ability of tobramycin to completely dissolve in aqueous media, tobramycin complexation with highly polar SO(4) (2-) salts that further assist dissolution, and ionic exchanges between VITOSS and the environment. Silicate-xerogel-encapsulated VITOSS eluted 60.65 and 61.31% of impregnated tobramycin, whereas non-silicate-xerogel-encapsulated VITOSS eluted approximately one-third less impregnated tobramycin, at 21.53 and 23.60%. These results suggest that silicate xerogel optimizes tobramycin elution because of its apparent biodegradability. This mechanism occurs through xerogel superficial acidic sites undergoing exchanges with various ions present in the leaching buffer. Tobramycin elution kinetics were evaluated, and demonstrate that first-order elution rate constants are considerably less when silicate xerogels are employed, following a more uniform exponential decay-type mechanism, thus bolstering controlled release. Overall, tobramycin elution rates adhere to linear-type Higuchi release profiles. Elution rate constants are initially first order, and taper into zero-order elution kinetics in the latter stages of release. Because VITOSS and silicate xerogel are completely biodegradable, essentially all impregnated tobramycin will be delivered to the surgical site after implantation.

Release of gentamicin from a tricalcium phosphate bone implant

“…Our results for aqueous-impregnated TCP samples are consistent with results of the study using tobramycin by DiCicco et al 9 As shown in Figure 2, only trace amounts of antibiotic are released after 2 days. This is likely due to the mechanism of gentamicin incorporation into the scaffold.…”

“…Initial first order kinetics were noted previously in the literature for tobramycin elution from TCP. 9 Thus, the elution rate is proportional to the concentration of gentamicin remaining in the implant, consistent with egress controlled by diffusion.…”

“…Iannuccelli et al studied gentamicin release from alginate beads in vitro 21 and in vivo. 22 The in vitro samples were tested without stirring, as was done by DiCicco et al 9 and in our experiments. In vitro, 80% of the gentamicin was released from high mannuronic acid alginate beads by day 3 and 100% in 2 weeks.…”

“…The first phase followed the protocol outlined by DiCicco et al, 9 whose study evaluated tobramycin elution after aqueous impregnation from the same TCP scaffold. According to this method, gentamicin-loaded TCP samples were immersed in phosphate buffered saline (PBS; pH 7.4; Mediatech, Herndon, VA) to a final volume of 45 mL (sample plus buffer) to create sink conditions, such that effusion was not limited by back-diffusion.…”

Injectable Biomaterials for Regenerating Complex Craniofacial Tissues

“…[140–143] The incorporation of other degradable particles such as poly(trimethyl carbonate) and gelatin microparticles has yielded similar favorable results within injectable formulations, [144, 145] and the potential for drug or growth factor release from these systems has been well demonstrated. [146–150] Including a water soluble porogen such as mannitol can both improve the injectability of CaP cement while also improving the flexural strength and toughness of the resulting scaffold. [151] Although not part of an injectable system, the incorporation of an absorbable polymer mesh within a CaP cement can also significantly increase the flexural strength and toughness of the material while resulting in macroporosity upon degradation of the network.…”