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Jae Hwan Jung, Bryce Chiang, Mark R Prausnitz; Electric field-mediated targeting of drug delivery in the suprachoroidal space. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4030.
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© ARVO (1962-2015); The Authors (2016-present)
Drug delivery to the suprachoroidal space (SCS) using a microneedle targets drugs to the choroid and adjacent retina. Although SCS delivery improves targeting to sites of drug action, further control of drug distribution within the SCS will enable more precise targeted of drug to, for example, the posterior pole. We hypothesize that application of an electric field within the SCS can drive charged molecules and particles, and thereby localize drug delivery to specific sites within the SCS.
A hollow microneedle with 30-gauge and 750µm length was used to inject negatively charged fluorescent particles into the SCS of the rabbit eye ex vivo. The syringe connected to the microneedle was modified by embedding a Ag/AgCl electrode in the chamber of syringe, which was connected to a DC power supply. When 100µL of the particle solution was infused into the SCS through the microneedle, electric current (0.05mA) was applied for 5min from the injection site to the optic nerve (ON), where another Ag/AgCl electrode was connected. To demonstrate the effect of the electric field on particle movement, experiments were carried out with both polarities of the electric field in order to direct particle transfer to either the anterior or posterior SCS. After the injection, particle distribution was analyzed. All cases were performed three times.
Particles injected into the SCS in the absence of an electric field were distributed more toward the anterior region, with 35–40% of particles in the most anterior quadrant of the SCS (i.e., <3mm from the limbus) and only ~15% of particles in the most posterior quadrant of the SCS (i.e., >9mm from the limbus). When 0.05mA of electric current was applied from the injection site to the ON, the particles were delivered more efficiently to the posterior SCS, with <30% of particles found in the most anterior quadrant and ~25% of particles found in the most posterior quadrant. In contrast, when the electric field polarity was switched, ~45% of the particles were found near the injection site in the most anterior quadrant and <5% of particles were in the most posterior quadrant.
Charged particles injected into the SCS were delivered more preferentially to the anterior or posterior portions of the SCS in the rabbit eye ex vivo according to the electric current and its polarity, which suggests a strategy for targeting drug delivery to specific regions within the SCS.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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