Device design methodology and formulation of a protein therapeutic for sustained release intraocular delivery.

Despite years of effort, sustained delivery of protein therapeutics remains an unmet need due to three primary challenges - dose, duration, and stability. The work presented here provides a design methodology for polycaprolactone reservoir-based thin film devices suitable for long-acting protein delivery to the back of the eye. First, the challenge of formulating highly concentrated protein in a device reservoir was addressed by improving stability with solubility-reducing excipients. Next, predictive correlations between design parameters and device performance were developed to provide a methodology to achieve a target product profile. Prototype devices were designed using this methodology to achieve desired device size, release rate, therapeutic payload, and protein stability, assessed by in vitro studies. Finally, prototype tolerability was established in a non-human primate model. The design methodology presented here is widely applicable to reservoir-based sustained delivery devices for proteins and provides a general device design framework.