(56b) On-Demand Delivery and Monitoring of Drug

Frequent injections are often needed for chronic diseases such as diabetic macular edema (in the posterior of the eye), or osteoarthritis (degenerative joint diseases). However, repeated injection is not only invasive and inconvenient for patients but also increases a risk of complications such as retinal detachment. Therefore, drug delivery systems that achieve longer duration of pharmacological effect with less frequent administration are urgently needed.

The long-term objectives of this study are to develop double emulsion nanodroplets that contain a drug and can be stably stored in the body for a long time and activated for drug release in a controlled manner with monitoring capability. The basic mechanism of controlled release from this drug-delivery system is to induce a phase transition of gold nanorod-coated nanodroplets by light (laser) utilizing plasmonic photothermal effect. The phase transition is monitored using ultrasound imaging, indicating the possibility of tracking drug release in vivo non-invasively.

Particle formulation has been optimized by altering shell composition to increase drug encapsulation capacity and stability against dissolution, aggregation, and drug leakage. Optical imaging and various spectroscopy methods were used to prove existence of gold nanorods on the shell and drug encapsulation. The nanodroplets were stable for months against aggregation and drug leakage at 4, 25, and 37 ºC in physiological conditions. Phase-transition with femto/pico second laser pulses was demonstrated by optical microscopy and ultrasound imaging. The nanodroplets were stored in ex-vivo eyes stable until there were phase-transitioned by laser, indicating controlled drug release. Real-time ultrasound imaging confirmed the phase-transition. Quantitative drug release was measured in vitro using fluorescence and ultrasound brightness intensity integration. In addition, in vitro studies with retinal pigment epithelial cells showed that targeted nanodroplets are non-toxic and effectively attach to the cells. Overall, these nanodroplets have potential to be used as image-monitored long-term controlled-release drug delivery system.