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A novel microfluidic tool for the evaluation of local drug delivery systems in simulated in vivo conditions
Lab on a Chip ( IF 6.1 ) Pub Date : 2024-07-24 , DOI: 10.1039/d4lc00181h William A Oates 1 , Antonios D Anastasiou 1
Lab on a Chip ( IF 6.1 ) Pub Date : 2024-07-24 , DOI: 10.1039/d4lc00181h William A Oates 1 , Antonios D Anastasiou 1
Affiliation
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A 3D-printed microfluidic tool for assessing local drug delivery systems (LDD) in simulated in vivo conditions was developed and evaluated. The device was designed considering the oral environment and dental applications, and it was fabricated with a high-precision resin 3D printer. Chitosan scaffolds loaded with different concentrations of doxycycline were used for evaluating our device. The concentration of the released drug was measured through in-line UV-VIS spectroscopy, and to verify the repeatability and accuracy of our measurements, comparisons with standard HPLC results were made (5% deviation). Cumulative drug release profiles in steady-state conditions were obtained and compared to the Weibull model. The behaviour of the LDD system in a dynamic environment was also evaluated during experiments where step changes in pH were introduced. It was demonstrated that under infection-like conditions, there is an immediate response from the polymer and a clear increase in the concentration of the released drug. Continuous flow and recirculation experiments were also conducted, revealing significant differences in the drug release profiles. Specifically, in the case of continuous flow, the quantity of the released drug is much higher due to the higher driving force for diffusion (concentration gradient). Overall, the proposed microfluidic tool proved to be ideal for evaluating LDD systems, as the in vivo microenvironment can be replicated in a better way than with currently used standard systems.
中文翻译：
一种新型微流体工具，用于在模拟体内条件下评估局部药物输送系统
开发并评估了一种 3D 打印微流体工具，用于在模拟体内条件下评估局部药物输送系统 (LDD)。该装置的设计考虑了口腔环境和牙科应用，并采用高精度树脂3D打印机制造。使用负载不同浓度强力霉素的壳聚糖支架来评估我们的装置。通过在线紫外可见分光光度计测量释放药物的浓度，并与标准 HPLC 结果进行比较（5% 偏差），以验证测量的重复性和准确性。获得稳态条件下的累积药物释放曲线并与威布尔模型进行比较。在引入 pH 阶跃变化的实验中，还评估了 LDD 系统在动态环境中的行为。事实证明，在类似感染的条件下，聚合物会立即做出反应，并且释放的药物浓度明显增加。还进行了连续流动和再循环实验，揭示了药物释放曲线的显着差异。具体而言，在连续流动的情况下，由于扩散驱动力（浓度梯度）较高，释放的药物量要高得多。总体而言，所提出的微流体工具被证明是评估 LDD 系统的理想选择，因为体内微环境可以比当前使用的标准系统更好的方式进行复制。
更新日期：2024-07-25
中文翻译：
一种新型微流体工具，用于在模拟体内条件下评估局部药物输送系统
开发并评估了一种 3D 打印微流体工具，用于在模拟体内条件下评估局部药物输送系统 (LDD)。该装置的设计考虑了口腔环境和牙科应用，并采用高精度树脂3D打印机制造。使用负载不同浓度强力霉素的壳聚糖支架来评估我们的装置。通过在线紫外可见分光光度计测量释放药物的浓度，并与标准 HPLC 结果进行比较（5% 偏差），以验证测量的重复性和准确性。获得稳态条件下的累积药物释放曲线并与威布尔模型进行比较。在引入 pH 阶跃变化的实验中，还评估了 LDD 系统在动态环境中的行为。事实证明，在类似感染的条件下，聚合物会立即做出反应，并且释放的药物浓度明显增加。还进行了连续流动和再循环实验，揭示了药物释放曲线的显着差异。具体而言，在连续流动的情况下，由于扩散驱动力（浓度梯度）较高，释放的药物量要高得多。总体而言，所提出的微流体工具被证明是评估 LDD 系统的理想选择，因为体内微环境可以比当前使用的标准系统更好的方式进行复制。
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