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

Journal of Korean Neurosurgical Society 2020년 63권 1호 p.45 ~ 55
신동원 ( Shin Dong-Won ) - Inje University College of Medicine Inje University Ilsan Paik Hospital Department of Neurological Surgery

손문준 ( Sohn Moon-Jun ) - Inje University College of Medicine Inje University Ilsan Paik Hospital Department of Neurological Surgery
조종래 ( Cho Chong-Rae ) - Inje University College of Medicine Inje University Ilsan Paik Hospital Department of Laboratory Medicine
 ( Koo Hae-Won ) - Inje University College of Medicine Inje University Ilsan Paik Hospital Department of Neurological Surgery
윤상원 ( Yoon Sang-Won ) - Inje University College of Medicine Inje University Ilsan Paik Hospital Department of Neurological Surgery

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.

키워드

Drug delivery system; Fibrin tissue adhesive; Disk diffusion antimicrobial tests; High-performance liquid chromatography; Surgical wound infection
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