School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
Biomater Adv. 2022 Aug;139:213024. doi: 10.1016/j.bioadv.2022.213024. Epub 2022 Jul 9.
Implantable drug delivery systems are an interesting alternative to conventional drug delivery systems to achieve local or systemic drug delivery. In this work, we investigated the potential of fused-deposition modelling to prepare reservoir-type implantable devices for sustained drug delivery. An antibiotic was chosen as a model molecule to evaluate the potential of this type of technology to prepare implants on-demand to provide prophylactic antimicrobial treatment after surgery. The first step was to prepare and characterize biodegradable rate-controlling porous membranes based on poly(lactic acid) (PLA) and poly(caprolactone) (PCL). These membranes were prepared using a solvent casting method. The resulting materials contained different PLA/PCL ratios. Cylindrical implants were 3D-printed vertically on top of the membranes. Tetracycline (TC) was loaded inside the implants and drug release was evaluated. The results suggested that membranes containing a PLA/PCL ratio of 50/50 provided drug release over periods of up to 25 days. On the other hand, membranes containing lower PCL content did not show a porous structure and accordingly the drug could not permeate to the same extent. The influence of different parameters on drug release was evaluated. It was established that film thickness, drug content and implant size are critical parameters as they have a direct influence on drug release kinetics. In all cases the implants were capable of providing drug release for at least 25 days. The antimicrobial properties of the implants were evaluated against E. coli and S. aureus. The resulting implants showed antimicrobial properties at day 0 and even after 21 days against both type of microorganisms. Finally, the biocompatibility of the implants was evaluated using endothelial cells. Cells exposed to implants were compared with a control group. There were no differences between both groups in terms of cell proliferation and morphology.
植入式药物输送系统是一种替代传统药物输送系统的有趣方法，可以实现局部或全身药物输送。在这项工作中，我们研究了熔融沉积建模在制备用于持续药物输送的储库型植入式装置方面的潜力。选择一种抗生素作为模型分子，以评估这种技术制备按需植入物的潜力，以便在手术后提供预防性抗菌治疗。第一步是使用溶剂浇铸法制备和表征基于聚乳酸（PLA）和聚己内酯（PCL）的可生物降解控释多孔膜。所得到的材料含有不同的 PLA/PCL 比。将圆柱形植入物垂直地 3D 打印在膜的顶部。将四环素（TC）加载到植入物内部，并评估药物释放。结果表明，含有 PLA/PCL 比为 50/50 的膜可在长达 25 天的时间内提供药物释放。另一方面，含有较低 PCL 含量的膜没有显示出多孔结构，因此药物不能渗透到相同程度。评估了不同参数对药物释放的影响。结果表明，膜厚度、药物含量和植入物尺寸是关键参数，因为它们直接影响药物释放动力学。在所有情况下，植入物都能够提供至少 25 天的药物释放。评估了植入物对大肠杆菌和金黄色葡萄球菌的抗菌性能。结果表明，植入物在第 0 天就具有抗菌性能，甚至在 21 天后对两种类型的微生物仍具有抗菌性能。最后，使用内皮细胞评估了植入物的生物相容性。将暴露于植入物的细胞与对照组进行比较。两组在细胞增殖和形态方面没有差异。
