Effect of ceramic carrier porosity and solubility on antimicrobial drug release in the local treatment of infections caused by periodontal pathogens and fungi

Relevance . Dysbiosis of the oral microbiome, with a predominance of anaerobic periodontal pathogens and Candida species, plays a key role in the pathogenesis of chronic periodontitis, peri-implantitis, and osteomyelitis of the jaws. Systemic antibiotic therapy is limited by poor penetration into bone and the risk of selecting for antibiotic resistance. Local drug delivery using calcium phosphate carriers can achieve exceptionally high drug concentrations at the infection site; however, selecting the optimal carrier requires an understanding of the physicochemical mechanisms of drug release. Objective . To determine how the release of metronidazole, ciprofloxacin, and fluconazole depends on the porosity and solubility of three types of ceramics: biogenic calcium phosphate ceramics (BCPC), hydroxyapatite (HA), and tricalcium phosphate (TCP), and to identify biologically appropriate drug–carrier combinations for microbiota modulation. Materials and methods . Disks made of BCPC (porosity, 33.7%), synthetic HA (24.5%), and TCP (26.0%) were impregnated with solutions of ciprofloxacin (2 mg/mL), metronidazole (5 mg/mL), and fluconazole (2 mg/mL). Drug release was assessed indirectly using an agar diffusion assay with test strains of Prevotella intermedia and Candida albicans ATCC 90028 (n = 24 per combination). Statistical analysis included one-way analysis of variance (ANOVA) with Tukey post hoc comparisons and Pearson correlation analysis. The experiments were conducted at Transgenbank, a unique research facility at the Institute of Gene Biology of the Russian Academy of Sciences, Russia. Results . For metronidazole and fluconazole, inhibition zone diameters showed an almost linear relationship with carrier porosity: BCPC > TCP > HA (30.40 > 25.16 > 24.14 mm for metronidazole; 22.16 > 19.08 > 17.98 mm for fluconazole; r = 0.997 and 0.990, respectively). Ciprofloxacin showed a different ranking: TCP > HA > BCPC (25.59 > 22.64 > 17.91 mm), owing to chelation of calcium ions and the solubility of the matrix. All between-group differences were statistically significant ( p < 0.001; η 2 = 0.899–0.947). Conclusion . The release of metronidazole and fluconazole is determined exclusively by pore volume, whereas carrier solubility is critical for ciprofloxacin. The recommended combinations are metronidazole–BCPC, ciprofloxacin–TCP, and fluconazole–BCPC. These patterns explain differences in the clinical effectiveness of the carriers and enable individualized local treatment based on microbiome composition.