Release Kinetics of Fluorescein Loaded Polymer Films

Pharmacological intervention in the brain is inhibited by the body’s natural filtration between the blood and the central nervous system (CNS) tissues. This enhanced selectivity is collectively known as the blood brain barrier (BBB). Further, systemic drug delivery results in equally distributed drug to non-target organs which can cause adverse effects. A promising alternative to systemic drug delivery is to utilize neural electrodes coated with electro-responsive conducting polymers. The neural electrode physically breaks through the BBB, and drug delivery is limited to the tissues directly adjacent to the device. Further, release of drug can be controlled by an electrical stimulus, allowing for temporal control of the delivered drug. This makes drug delivery from neural electrodes a promising tool to deliver therapeutics to the CNS tissues. Despite these advantages, the release kinetics of conducting polymers is still poorly understood. Here we developed a method to investigate how long drug can be released following electrochemical stimulations.

Methods:

Poly 3,4- Ethylenedioxythiophene (PEDOT) was deposited onto 2mm gold electrodes by submerging the electrode in a 0.01M ethylenedioxythiophene solution saturated with fluorescein and applying 10uA over 10 minutes. After the electrodes were coated, we released the fluorescein through 20 cyclic voltammetry (CV) sweeps from 0.6V to -0.8V vs Ag/AgCl at 100mV s-1. Fluorescein was released into phosphate buffered saline solution. Detection of fluorescein was done with the use of fluorescent microscopy which was calibrated with specific molar concentrations. These readings were taken before the CV sweeps, after 10 sweeps, after 20 sweeps, and then multiple time points were measure until no additional release was observed.

Conclusion:

Through these trials it was found that most release occurs in the first 10 sweeps of CV, which we believe can be a variety of factors: the adsorption of fluorescein to the polymer film, and ease of release of fluorescein higher up in the polymer matrix. It was expected that post-stimulatory diffusion would cease within minutes after then end of stimulation, however, on average it lasted over 500 minutes. These results demonstrate that drug release from conducting polymers occurs over substantially longer periods than previously believed, and longer sampling windows will allow for better understanding of the release kinetics of fluorescein from conducting polymers.