UCSF

This dissertation covers the use of several types of polymer thin films for sustained drug delivery in the back of the eye (BOTE) and the peripheral vasculature. In general, the thin films are combined around a drug payload to restrict its release into the surrounding in vitro or in vivo environment. The polymer films make use of micro- and nanotechnology to control the release behavior of the various drugs they encapsulate. All devices aim to enable or extend the delivery of therapeutics to their target site of action.

The first device presented uses polycaprolactone (PCL) thin films to encapsulate rapamycin. The device achieves sustained release of rapamycin to the retina, while also possessing the ability to modulate release of the drug by changing the thickness of the films.

A second drug delivery device here presented uses nanoporous PCL thin films to control the release of the large molecule therapeutic ranibizumab from the device. The nanopores of this PCL device work to restrict the diffusion of the drug through the films and results in a detectable concentration of ranibizumab in the vitreous up to 12 weeks.

The third device type described here uses varying compositions of PLGA films to achieve unidirectional, sustained, and local release of the specialized pro-resolving mediator RvD1 for surgical applications. The thin film layers of PLGA are combined to create a drug-eluting wrap that can be wrapped around sites of vascular surgery to limit post-surgical inflammation.

These demonstrations illustrate the diverse therapeutic areas where biodegradable polymer thin films may improve pharmacokinetics, patient quality of life, and overall outcomes. Across the spectrum of small to large molecules and the many target site for drug delivery in the body, polymer thin films can be used in a variety of advanced devices to solve the challenges of medicine.