Editors' ChoiceNanomedicine

Golden Cage for Triggered Release

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Science Translational Medicine  12 Feb 2014:
Vol. 6, Issue 223, pp. 223ec27
DOI: 10.1126/scitranslmed.3008642

A chip implanted under the skin and activated by remote control—science fiction or already here? Timely release of drugs according to need is the next step in material design. Such release devices will reduce drug toxicity and increase effectiveness. Although triggered-release devices aiming to control drug dose and timing recently became available, they still lack control over the release pattern and the on/off release ratio and present poor reproducibility over multiple release cycles. Yet, some illnesses are better treated periodically, requiring an irregular release profile. In a paper by Timko et al., the authors report a drug reservoir capped with a porous membrane whose permeability is externally tunable, allowing triggered sustained or pulsatile release of embedded drugs.

To make this device, a membrane composed of hydrophobic ethylcellulose matrix was embedded with gold nanoparticles and a mixture of three different acrylamide-based monomers, creating thermosensitive nanogels. When the gold nanoparticles absorb near-infrared light (808 nm), the resulting generation of heat at the site collapses the network of polymeric nanogels at a temperature slightly above 37°C and permits drug release through the membrane. After the light source is removed, the membrane reforms, blocking further release. The nanogel particles’ diameter reversibly changes from 800 to <100 nm as a function of temperature, determining the release pattern. Diabetic rats were implanted with devices containing a synthetic form of insulin, aspart, whose release was triggered by exposure to laser light. The devices could be retriggered every day for at least 5 days and continued to release more medicine, titrated to the blood glucose concentration. Repeated dosing was demonstrated by 30-min dosing cycles triggered by laser irradiation, with an on/off ratio of 30 between drug released in the presence or absence of external stimuli.

The design of tunable devices with a dynamic range of release kinetics that can be matched to specific indications presents an important advance in the field of triggered release. Although it is promising in preclinical models, the authors still need to examine the long-term safety, dosing, and clinical efficacy of this technology. The system needs to be optimized for a lower triggering threshold and shorter irradiation times in order to avoid laser burns after repeated irradiation cycles. In addition, a fully resorbable device may need to be developed for better clinical adoption.

B. P. Timko et al., Near-infrared–actuated devices for remotely controlled drug delivery. Proc. Natl. Acad. Sci. U.S.A., published online 28 January 2014 (10.1073/pnas.1322651111). [Abstract]

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