Faculty of Engineering, Department of Chemical Engineering, King Mongkut's University of Technology Thonburi, Bangkok, Thailand.
Faculty of Engineering, Biological Engineering Program, King Mongkut's University of Technology Thonburi, Bangkok, Thailand.
PLoS One. 2024 Nov 1;19(11):e0311521. doi: 10.1371/journal.pone.0311521. eCollection 2024.
This study aimed to develop a mathematical model to predict the release profile and antibacterial efficacy of a vancomycin delivery system integrated with poly(L-lactic acid)-coated bone implants specifically designed for bone plates. Using Fickian diffusion principles within an ANSYS-CFX computational fluid dynamic model, we validated the model against our in vitro vancomycin release and agar diffusion studies, as well as previously published in vivo data, confirming the reliability of the model. The model predictions demonstrated the effectiveness of the system in inhibiting bacterial growth in surrounding tissue with no observed toxicity, with a peak vancomycin concentration of 0.95 mg/ml at 6 hours, followed by a decrease to levels that remained effective for antibacterial activity. Furthermore, a sensitivity analysis revealed that the model is particularly sensitive to the half-life of vancomycin, with a maximum sensitivity index of 0.8, indicating its greater impact on the prediction accuracy than the diffusion coefficient, which has a maximum sensitivity index of 0.5. Therefore, precise input of vancomycin's half-life is critical for accurate predictions. These findings offer substantial support for the efficacy of the local delivery system as a promising therapeutic approach against implant-associated infections.
本研究旨在开发一个数学模型，以预测一种万古霉素输送系统的释放曲线和抗菌效果，该系统与专门设计用于骨板的聚（L-乳酸）涂层骨植入物相结合。我们使用 ANSYS-CFX 计算流体动力学模型中的菲克扩散原理，将模型与我们的万古霉素体外释放和琼脂扩散研究以及先前发表的体内数据进行了验证，证实了模型的可靠性。模型预测表明，该系统在抑制周围组织中的细菌生长方面非常有效，且没有观察到毒性，6 小时时的万古霉素峰值浓度为 0.95mg/ml，随后降至仍具有抗菌活性的水平。此外，敏感性分析表明，该模型对万古霉素半衰期特别敏感，最大敏感性指数为 0.8，表明其对预测准确性的影响大于扩散系数，扩散系数的最大敏感性指数为 0.5。因此，准确输入万古霉素的半衰期对于准确预测至关重要。这些发现为局部输送系统作为对抗植入物相关感染的一种有前途的治疗方法的疗效提供了有力支持。
