Near-infrared-actuated devices for remotely controlled drug delivery
Near-infrared-actuated devices for remotely controlled drug delivery
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DOI：
10.1073/pnas.1322651111
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发表时间：
2014-01-28
影响因子：
11.1
通讯作者：
Kohane, Daniel S.
中科院分区：
文献类型：
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作者：
Timko, Brian P.;Arruebo, Manuel;Kohane, Daniel S.
可以远程触发以释放药物的储器将使患者或医生能够实现按需、可再现、重复和可调的给药。这样的装置将允许精确地调节剂量以达到期望的效果，从而使毒性最小化，并且可以避免重复的药物施用或装置更换，从而增强患者的依从性。它应该表现出低的关闭状态泄漏，以最大限度地减少基础效应，和可调的开状态释放曲线，可以从脉动调整到持续的真实的时间。尽管临床上明确需要符合这些标准的器械，但据我们所知，迄今为止还没有报告。为了解决这一缺陷，我们开发了一种可植入的水库覆盖的纳米复合材料膜的渗透性调制的近红外激光照射。经辐照的装置可表现出持续的开状态药物释放至少3小时，并且可在至少10个周期内可再现地递送短脉冲，开/关比为30。含有速效胰岛素类似物门冬胰岛素的装置，可以在皮下注射后达到血糖控制。植入糖尿病大鼠，可重复的剂量控制的强度和时间的照射超过2周的时间。这些器械可装载多种药物类型，因此代表了可用于解决多种临床适应症的平台技术。
A reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time. Despite the clear clinical need for a device that meets these criteria, none has been reported to date to our knowledge. To address this deficiency, we developed an implantable reservoir capped by a nanocomposite membrane whose permeability was modulated by irradiation with a near-infrared laser. Irradiated devices could exhibit sustained on-state drug release for at least 3 h, and could reproducibly deliver short pulses over at least 10 cycles, with an on/off ratio of 30. Devices containing aspart, a fast-acting insulin analog, could achieve glycemic control after s.c. implantation in diabetic rats, with reproducible dosing controlled by the intensity and timing of irradiation over a 2-wk period. These devices can be loaded with a wide range of drug types, and therefore represent a platform technology that might be used to address a wide variety of clinical indications.