This research analyzed Tobramycin and Gentamycin elution characteristics for two antibiotic-impregnated bone composites: PMMA-based Simplex P and the novel, hybrid, bioactive, CORTOSS. Experimental results were correlated with composite hydrophilicity and antibiotic phase partitioning behaviors. The phase partitioning experiment was conducted to understand antibiotic solubility in aqueous environments. By comparing experimental results with calculated data, antibiotic release behavior was predicted. Total Tobramycin elution percentages from CORTOSS and Simplex P were 12.5 and 6.4%, respectively. Total Gentamycin elution percentages from CORTOSS and Simplex P were 6.95 and 10.17%, respectively. Phase partitioning data indicate 100% of Tobramycin remains in aqueous phases, being extremely hydrophilic. This is supported by its calculated theoretical value (log P = - 7.32). Results suggest that Tobramycin elution can be attributed to composite hydrophilicity as well as its high degree of hydrophilicity. Fifteen percent of Gentamycin distributes in hydrophobic phases (log P = - 4.22). Despite a lower Gentamycin hydrophilicity, its release was affected by its complexation with polar salts in the leaching buffer, thereby increasing its elution potential, making it appreciably water soluble. CORTOSS is more hydrophilic; therefore the migration of aqueous liquids into the polymer network of CORTOSS facilitates greater antibiotic elution compared with hydrophobic Simplex P.

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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.

Hydroxyl radical (⅐OH)-induced inflammation is a primary mode for in vivo cytotoxicity. A legitimate concern is whether particulate wear debris from orthopedic composites can stimulate inflammation via ferrous ion (Fe 2؉ )-mediated production of ⅐OH. The purpose of this research was to utilize electron paramagnetic resonance (EPR) spin trapping in investigating and comparing the potential for postsurgical cytotoxicity induced specifically by ⅐OH in the presence of two composites: Simplex P and the novel, hybrid, CORTOSS™. Cytotoxicity is evaluated based on the composites competitively chelating catalytic Fe 2؉ or readily reducing ferric ions (Fe 3؉ ), in facilitating the Fenton reaction (FR). ⅐OH that are produced were then validated by a radical scavenger to confirm a genuine radical signal and mechanism. Spin adduct peak areas decreased in the presence of CORTOSS as opposed to increasing in the presence of Simplex P, evaluated against their respective controls. A plausible theory elucidating this finding is that CORTOSS may sequester the Fe form, by virtue of its monomers. Principally, direct comparison of composites indicated that Simplex P had greater tendency to produce ⅐OH, yielding 25.6 and 48.7% greater spin adduct peak areas when chelated and non-chelated Fe 2؉ are used, respectively. Moreover, the rate of FR accelerated when chelated Fe 2؉ was used, leading to the formation of a ternary complex with the composites. This was more prominent in Simplex P, as coordination of chelated Fe 2؉ occurs on its surface via an electrostatic attraction to allow a seventh coordination site for ligand exchange in the ternary complex, stabilized by Ba 2؉ . Conversely, the silica found in CORTOSS possesses radical quenching abilities that deactivate generated ⅐OH in impeding the efficiency of FR. Neither composite demonstrated a capacity to readily reduce Fe 3؉ to the relevant Fe 2؉ , as validated by a non-radical pathway. Instead, the artificial spin adduct signal attained when employing chelated Fe 3؉ was due to the nucleophilic addition of water onto DMPO. Simplex P may also serve as a template for surface catalysis of the nucleophilic addition of water onto DMPO involving chelated Fe 3؉ . CORTOSS is thought not to induce cytotoxicity, whereas the propensity of Simplex P in promoting Fenton chemistry is a serious issue that must be addressed.

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