(L-479) Developing a Method to Characterize and Characterize Drug-Release Profiles Under Biologically-Relevant Conditions

Intracortical neural interfaces have become well known for their ability to be incorporated in systems that restore motor, sensory and cognitive functions to individuals affected by neurological disease or injury. However, when these neural probes are implanted in the brain, the neuroinflammatory response cause both biological and material failure [1].

Nanoporous materials have become an alternative for local delivery implemented in implantable devices. The biocompatibility of metal oxide nanotubes as well as their stable cylinder shape allow them to be a good candidate for drug delivery vehicle due to their ability to store drug molecules and control their release. Microvolume spectrophotometry was used previously to monitor drug release rates under static conditions (no flow) by detecting changes in reflected light as the drug is released from the nanotubes when added into a saline solution [2]. However, this method operates under a finite sink condition that does not match conditions in the brain [3]. The current study focuses on characterizing the drug release of anti-inflammatory dexamethasone in titania nanotube arrays (TNAs) in both static (no flow) and dynamic conditions in a flow cell. This study represents a significant advancement towards the development of a precise method for controlling the drug release profiles of dexamethasone in TNAs, offering promising opportunities for its implementation in neural probes.

For static and dynamic conditions, we hypothesized that reflectance spectroscopy would allow us to quantify and relate reflectance intensity to drug contained within or released from TNAs. The main purpose of static release experiments in phosphate buffered saline PBS, was to understand the drug-release contributions to spectral reflectance. The purpose of dynamic flow-through condition experiments, was to develop a system that can mimic drug elimination profiles in the brain so that release profiles can be characterized. When carrying out these experiments, it was expected that spectral reflectance would vary with the amount of drug loaded in the TNAs that would later help to create a relation between unreleased drug remaining in the TNAs and the reflected light intensity.

The experimental conditions for static release included placing a loaded TNA sample into a petri dish filled with 5mL of PBS and making spectral reflectance measurements over an 8 hours duration using a Filmetrics spectral reflectance instrument. For the dynamic conditions, a tungsten-halogen-lamp light source served as light source and an Ocean Optics USB4000 spectrometer were directed at the sample using a fiber optic probe. The sample was mounted in a custom 3D-printed flow cell. Reflectance spectra were acquired every 1 to 5 minutes using MATLAB while flowing PBS through the flow cell at 1ml/h for 24 hours. The effects of PBS height above the sample and of cover slip material used as a window through the flow cell and into the sample were determined and optimized in the flow cell design.

Results

For the static conditions, it was found that, spectral reflectance increased and remained steady as drug was released in PBS, which can be seen in Figure 1. For dynamic conditions, the reflectance intensity decreased over the duration of the experiment as seen in Figure 2.

Discussion

There was a relationship seen in both static in dynamic conditions that linked drug released with reflectance and intensity values and it was proportional to the amount of drug released over time. For the flow cell in the dynamic conditions, it was found that cover slips reflect some of the incident light, thereby affecting the sensitivity of the measurement. This effect was less pronounced with the glass cover slip than a plastic cover slip window, leading us to choose glass cover slip windows in the flow cells for the experimental conditions. Next steps involve the study of drug release under varying flow rates, as well as investigating a variety of drugs loaded into the TNAs.

Conclusions

Reflectance spectroscopy does play a key role in quantifying drug released in both experimental conditions. It was demonstrated that changes in drug concentration in the solution were detected by both methods. Both methods showed a relationship of capacity loaded in sample with its reflectance and intensity values.

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