Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Clin Ther. 2012 Nov;34(11):S25-35. doi: 10.1016/j.clinthera.2012.09.012.
Technologies in which a remote trigger is used to release drug from an implanted or injected device could enable on-demand release profiles that enhance therapeutic effectiveness or reduce systemic toxicity. A number of new materials have been developed that exhibit sensitivity to light, ultrasound, or electrical or magnetic fields. Delivery systems that incorporate these materials might be triggered externally by the patient, parent or physician to provide flexible control of dose magnitude and timing.
To review injectable or implantable systems that are candidates for translation to the clinic, or ones that have already undergone clinical trials. Also considered are applicability in pediatrics and prospects for the future of drug delivery systems.
We performed literature searches of the PubMed and Science Citation Index databases for articles in English that reported triggerable drug delivery devices, and for articles reporting related materials and concepts.
Approaches to remotely-triggered systems that have clinical potential were identified. Ideally, these systems have been engineered to exhibit controlled on-state release kinetics, low baseline leak rates, and reproducible dosing across multiple cycles.
Advances in remotely-triggered drug delivery have been brought about by the convergence of numerous scientific and engineering disciplines, and this convergence is likely to play an important part in the current trend to develop systems that provide more than one therapeutic modality. Preclinical systems must be carefully assessed for biocompatibility, and engineered to ensure pharmacokinetics within the therapeutic window. Future drug delivery systems may incorporate additional modalities, such as closed-loop sensing or onboard power generation, enabling more sophisticated drug delivery regimens.
使用远程触发器从植入或注射装置中释放药物的技术可以实现按需释放的特性,从而提高治疗效果或降低系统毒性。已经开发出许多对光、超声、电磁场敏感的新材料。将这些材料结合在一起的输送系统可以由患者、家长或医生进行外部触发,从而灵活控制剂量大小和时间。
回顾可转化为临床应用的可注射或可植入系统,或已经进行临床试验的系统。还考虑了在儿科中的适用性以及药物输送系统的未来前景。
我们在 PubMed 和科学引文索引数据库中进行了英文文献检索,以查找报告可触发药物输送装置的文章,以及报告相关材料和概念的文章。
确定了具有临床潜力的远程触发系统的方法。理想情况下,这些系统经过设计,可以表现出受控的开启状态释放动力学、低基线泄漏率以及在多个循环中具有可重现的剂量。
远程触发药物输送的进展是许多科学和工程学科融合的结果,这种融合很可能在当前开发提供多种治疗模式的系统的趋势中发挥重要作用。临床前系统必须仔细评估其生物相容性,并进行工程设计以确保在治疗窗内的药代动力学。未来的药物输送系统可能会纳入其他模式,如闭环传感或板载发电,从而实现更复杂的药物输送方案。