Evaluation of Cumulative and Conditional Antibiotic Release from Vancomycin-Embedded Fibrin Sealant and Its Antibacterial Activity : An In Vitro Study

Abstract

Objective : Fibrin sealants have been used for hemostasis, sealant for cerebrospinal fluid leakage, and adhesive barrier in neurosurgery. Further, as its clinical use and role of an effective drug delivery vehicle have been proposed. This study was performed to measure antibacterial activity and continuous local antibiotic release from different concentrations of vancomycin-impregnated fibrin sealant in vitro. Methods : Antibacterial activity was investigated by disk diffusion test by measuring the diameter of the growth inhibition zone of bacteria (methicillin-resistant Staphylococcus aureus, ATCC29213) from vancomycin-embedded fibrin sealant disc diluted at five different concentrations (C1-C5; 8.33, 4.167, 0.83, 0.083, and 0.0083 mg/disc, respectively). Continuous and conditioned release of vancomycin concentration (for 2 weeks and for 5 days, respectively) were also measured using high-performance liquid chromatography (HPLC) method. To mimic the physiologic wound conditions with in vitro, conditioned vancomycin release in phosphate buffer solution (PBS) was measured and replaced PBS for five consecutive days, half a day or completely daily. Results : In the disk diffusion test, the mean diameters of bacterial inhibition zone were 2.54±0.07 cm, 2.61±0.12 cm, and 2.13±0.15 cm (C1, C2, and C3 respectively) but 1.67±0.06 cm and 1.23±0.15 cm in C4 and C5, respectively. Continuous elution test elicited the peak release of vancomycin from the fibrin sealant at 48 hours, with continued release until 2 weeks. However, conditioned vancomycin release decreased to half or more on day 2, however, the sustainable release was measured over the therapeutic dose (10-20 µg/mL) for 5 days and 4 days in assays of half and total exchange of PBS. Conclusion : This study suggests that fibrin sealant can provide an efficient vehicle for antibiotic drug release in a wide range of neurosurgical procedures and the safe and effective therapeutic dose will be at the concentration embedded of 4.167 mg/disc or more of vancomycin.

Porous Polymer Scaffolds based on Cross‐Linked Poly‐EGDMA and PLA: Manufacture, Antibiotics Encapsulation, and In Vitro Study

“…[ 34 ] To determine the bactericidal activity of polymer materials, the disk‐diffusion method was used. [ 35 ] The disk diffusion test was used for the determination of the bactericidal activity of the polymers. Clean cultures of staphylococci sensitive to gentamicin ( Staphylococcus epidermidis 4743) and vancomycin ( Staphylococcus aureus 4766, Staphylococcus aureus 172) were used.…”

Antimicrobial Activity of Composites-Based on Biopolymers

“…Vancomycin impregnated fibrin sealant was developed to measure antibacterial activity and antibiotic release. This study uses fibrin sealant as a topical hemostat for post-operatory treatments in surgical fields [126]. AgNPs were studied in metal/fibrin nanocomposites, recognized as suitable materials for wound healing.…”

Fibrin glues — the current state of knowledge

“…The study also assessed sustained vancomycin release from fibrin and disc diffusion assays were performed to detect vancomycin-resistant Staphylococcus aureus MRSA. Vancomycin release from fibrin glue lasted 14 days and the antibacterial activity was strong throughout the period [24]. It must be noted however that antibiotics added to components of fibrin glue may alter the physical properties of fibrin, e.g.…”

“…The study of Kram et al demonstrated that gentamicin and neomycin extend clotting time. In conclusion, the properties of the clot as well as time of clot formation should always be checked in laboratory setting before using fibrin glue as a drug delivery system [7,14,[23][24][25].…”