Nanostructured Polymers for Delivery of Protein-based Therapeutics
Featuring Daniel A. Bernards, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco
There is a need for sustained drug release devices that are highly efficacious for delivery of protein-based therapeutics. Contemporary delivery routes, such as injections, are hampered by patient compliance, discomfort, risk, and inconvenience, as well as limited bioavailability and frequent administration. For instance, the recently developed drug ranibizumab (Lucentis, Genentech, Inc.) has made dramatic impacts in treating age-related macular degeneration, yet its benefits are tempered by a schedule of monthly intravitreal injections over the course of years. Alternatively, a therapeutic device capable of delivering a constant rate of drug over time can circumvent these drawbacks. One attractive platform for such a device is the use of nanoporous materials. In porous materials, constant-rate diffusion is possible when the size of a diffusing species is comparable to material pore size. A process often referred to as “single-file” diffusion, this situation can lead to zero-order constant-rate release. With pore size scaled appropriately to the protein of interest, this technology is compatible with essentially any protein therapeutic where zero-order delivery is advantageous. For delivery of typical macromolecules, pore size on the order of a few tens of nanometers is required.
To this end, nanoporous biodegradable thin film devices have been fabricated for delivery of protein therapeutics. While these flexible devices have applications in a variety of localized delivery applications, proof-of-concept devices have targeted ocular delivery of ranibizumab for treatment of age-related macular degeneration. These devices utilize biodegradable poly(caprolactone) thin films with transport-controlling nanostructures as well as microstructures for structural robustness. Designed as flexible biodegradable thin films, devices can be introduced via minimally invasive implantation or injection and subsequently biodegraded naturally. Long-term release from these devices has been investigated for a range of model therapeutics including ranibizumab. In addition, preliminary studies with rabbits have been undertaken to establish the long-term biocompatibility, structural integrity, bioresorption, and functionality of these devices upon implantation or injection. We believe that such devices will increase the efficacy of established antibody-based therapeutics and improve disease outcomes. Furthermore, because this technology is a device rather than a therapeutic, the advances established by this work are broadly applicable to the delivery of protein-based therapeutics.
Dr. Daniel Bernards is currently a postdoctoral scholar at the University of California at San Francisco working in the research group of Tejal Desai, where his research has focused on the development of nanostructured materials for drug delivery. In 2007, he received his PhD in Materials Science and Engineering at Cornell University working in the research group of George Malliaras, where his research focused on the interplay between ionic and electronic charge in a variety of organic semiconductor devices, including light emitting devices, photovoltaics, electrochemical transistors, and biosensors. In 2004 he was awarded a National Defense Science and Engineering Graduate Fellowship, and in 2009 he was the recipient of a Genentech Postdoctoral Fellowship Award.