Cirilli Micol, Krause Julius, Gazzaniga Andrea, Weitschies Werner, Cerea Matteo, Rosenbaum Christoph
Department of Pharmaceutical Sciences, University of Milan, GazzaLaB, via Giuseppe Colombo 71, 20133 Milan, Italy.
Department of Biopharmaceutics and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, Felix-Hausdorff-Strasse 3, 17489 Greifswald, Germany.
Pharmaceutics. 2024 Dec 27;17(1):29. doi: 10.3390/pharmaceutics17010029.
The development of targeted drug delivery systems for active pharmaceutical ingredients with narrow absorption windows is crucial for improving their bioavailability. This study proposes a novel 3D-printed expandable drug delivery system designed to precisely administer drugs to the upper small intestine, where absorption is most efficient. The aim was to design, prototype, and evaluate the system's functionality for organ retention and targeted drug release. The system was created using 3D printing technologies, specifically FDM and SLA, with materials such as PLA and HPMC. The device was composed of matrices and springs, with different spring geometries (diameter, coil number, and cross-sectional shape) being tested for strength and flexibility. A gastro-resistant string was used to maintain the device in a compact configuration until it reached the neutral pH environment of the small intestine, where the string dissolved. The mechanical performance of the springs was evaluated using a texture analyzer, and the ability of the system to expand upon pH change was tested in simulated gastrointestinal conditions. The results demonstrated that the system remained in the space-saving configuration for two hours under acidic conditions. Upon a pH change to 6.8, the system expanded as expected, with opening times of 5.5 ± 1.2 min for smaller springs and 2.5 ± 0.3 min for larger springs. The device was able to regain its expanded state, suggesting its potential for controlled drug release in the small intestine. This prototype represents a promising approach for targeted drug delivery to the upper small intestine, offering a potential alternative for drugs with narrow absorption windows. While the results are promising, further in vivo studies are necessary to assess the system's clinical potential and mechanical stability in real gastrointestinal conditions.
开发针对吸收窗窄的活性药物成分的靶向给药系统对于提高其生物利用度至关重要。本研究提出了一种新型的3D打印可膨胀给药系统，旨在将药物精确地输送到小肠上段，此处吸收效率最高。目的是设计、制作该系统的原型并评估其在器官滞留和靶向药物释放方面的功能。该系统是使用3D打印技术，特别是熔融沉积成型（FDM）和立体光刻（SLA），以及聚乳酸（PLA）和羟丙基甲基纤维素（HPMC）等材料制作而成。该装置由基质和弹簧组成，测试了不同弹簧几何形状（直径、圈数和横截面形状）的强度和柔韧性。使用一种耐胃酸的线将装置保持在紧凑结构中，直到其到达小肠的中性pH环境，此时线会溶解。使用质地分析仪评估弹簧的机械性能，并在模拟胃肠道条件下测试系统在pH变化时的膨胀能力。结果表明，该系统在酸性条件下在节省空间的结构中保持两小时。当pH值变为6.8时，系统如预期那样膨胀，较小弹簧的打开时间为5.5±1.2分钟，较大弹簧的打开时间为2.5±0.3分钟。该装置能够恢复其膨胀状态，表明其在小肠中控制药物释放的潜力。这个原型代表了一种有前景的将药物靶向递送至小肠上段的方法，为吸收窗窄的药物提供了一种潜在的替代方案。虽然结果很有前景，但还需要进一步的体内研究来评估该系统在实际胃肠道条件下的临床潜力和机械稳定性。
