Sustained delivery of protein therapeutics remains a
largely unsolved
problem across anatomic locations. Miniaturized devices that can provide
sustained delivery of protein formulations have the potential to address
this challenge via minimally invasive administration. In particular,
methodologies that can optimize protein formulation independent of
device manufacture have the greatest potential to provide a platform
suitable for wide applications. The techniques developed here demonstrate
the fabrication of tubular devices for sustained release of protein
therapeutics. Utilizing a dip-casting process, fine-scale tubes can
be reliably produced with wall thickness down to 30 μm. Techniques
were developed that enabled effective loading of either solid or liquid
formulations, while maintaining a cylindrical form-factor compatible
with placement in a 22-gauge needle. Further, highly compacted protein
pellets that approach the expected density of the raw materials were
produced with a diameter (∼300 μm) suitable for miniaturized
devices. Release from a solid-loaded device was capable of sustaining
release of a model protein in excess of 400 days. Given significant
interest in ocular applications, intravitreal injection was demonstrated
in a rabbit model with these devices. In addition, to simulate repeated
injections in ocular applications, serial intravitreal injection of
two devices in a rabbit model demonstrated acceptable ocular safety
without significant intraocular inflammation from clinical exam and
histology.