(446b) Dose-Controllable Light-Activated Drug Release Systems

Drug delivery systems for temporal and spatial drug release using nanocarriers, or so-called on-demand drug delivery systems, are a new therapeutic approach in the medicinal field. Not only can drug release be tightly controlled and negative side effects associated with incorrect dosage minimized, but also the therapeutic efficacy can be prolonged by conserving drug when not needed.^1-2 A photoactive-triggering mechanism of site-specific drug delivery has gained interest within this field of research.^3-4 Although the technique shows potential for repeatable on-demand drug delivery, the lack of understanding of nanostructural changes of the drug-carriers with various parameters of light activation often limit repeated application.

Here we report on novel plasmonic material-coated liposomes (of mixed lipids) for the efficient delivery of methotrexate (MTX), a common drug for cancer and autoimmune diseases. Gold nanorods are used as the plasmonic material on the liposomes, which generate heat during near-infrared laser irradiation. The repetitive drug release from these MTX-encapsulated liposomes was measured using UV-Vis spectroscopy. The reversibility of the liposome structure after repetitive laser irradiation was determined using a single particle electrochemical measurements which measures the frequency of liposome collision events via changes in current that occur when a liposome collides with, and blocks, an electrode surface (2 μm diameter Pt disk).

We find that drug release occurs with each repetitive laser irradiation, whereas the liposome collision frequency (and thus concentration of liposomes) does not change. The collision frequencies of the irradiated liposomes were 0.056 Hz, 0.060 Hz and 0.060 Hz for 0 s, 30 s and 120 s irradiation time, respectively (1.9 W average power) indicating that the liposomes remain intact after irradiation. However, when MTX-encapsulated nanodroplets that underwent phase-transition from liquid to gas bubbles⁵ were irradiated, the collision frequencies were 0.13 Hz, 0.107 Hz and 0.023 Hz, for 0 s, 30 s and 120 s, respectively, demonstrating 18% and 82% decrease in collision frequencies for 30 s and 120 s irradiation, respectively. The results indicate the number density after irradiation was maintained for the liposomes but not for the nanodroplets, suggesting reversibility of the liposome structure.

When larger liposomes (mean 3 μm in diameter) were irradiated, the mean current drop per collision increased from 0.2 nA to 0.8 nA, compared to the regular liposomes tested above (230 nm in average diameter). However, the collision frequencies were 0.093 Hz, 0.09 Hz, and 0.103 Hz for 0 s, 30 s and 120 s, respectively, again indicative of the structure reversibility.

The results suggest that the gold nanorod-coated liposomes can be a potential drug carrier for repetitive on-demand drug delivery. In addition, we expect to measure drug dosage released from an individual carrier, leading to precise control of dosage multiple times for long term drug delivery.