Getting promising biological therapeutics to the desired location in the body in a safe and effective fashion is one of the key challenges in medicine. Many different disease states are now being targeted for treatment with biologicals including oncology, autoimmune, inflammatory, metabolic, cardiovascular, neurological, and ophthalmologic. In addition, it is anticipated that biological therapies will play a major role in the treatment of pain and for the use in anti-infective, anti-bacterial, anti-viral and anti-fungal treatments. However, despite the opportunity, there are significant road blocks that stand in the way to realizing the full potential of biological therapeutics and vaccines including: i) the need to dramatically improve circulation times;ii) the inability to tailor pharmacokinetics using simple injections or oral delivery; iii) the inability to deliver biologicals via pulmonary routes;iv) the inability of many biologicals to access intracellular targets;and v) the inability to deliver biologicals to poorly-vascularized tissues. Herein I propose to evolve emerging top-down particle fabrication technologies to make 2-dimensional arrays and free flowing powders of shape specific micro- and nano-particles that are comprised of almost pure biological molecules. Using patterned thin film based lyophilization processes that have very high rates of thermal and mass transport, ?solid state solutions? of particles comprised of biological molecules will be synthesized to control how quickly the molded particles will dissolve or how quickly the biological molecules within the particles will be released. In addition, I propose to exploit the unique 2-dimensional array format and the formation of free flowing powders of shape controlled biological therapeutics and vaccines to develop three novel dosage forms including: i) delivery via highly concentrated dispersions (alternative to solutions);ii) pulmonary delivery via inhalation;and iii) novel endoscopic and intravascular medical devices which use nanoparticle mediated ionotophoretic / electrophoretic methods to deliver biologicals to poorly vascularized tissues.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
8DP1CA174425-04
Application #
8318171
Study Section
Special Emphasis Panel (ZGM1-NDPA-B (02))
Program Officer
Fu, Yali
Project Start
2009-09-30
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$732,600
Indirect Cost
$237,600
Name
University of North Carolina Chapel Hill
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Roberts, Reid A; Shen, Tammy; Allen, Irving C et al. (2013) Analysis of the murine immune response to pulmonary delivery of precisely fabricated nano- and microscale particles. PLoS One 8:e62115
Parrott, Matthew C; Finniss, Mathew; Luft, J Chris et al. (2012) Incorporation and controlled release of silyl ether prodrugs from PRINT nanoparticles. J Am Chem Soc 134:7978-82
Dunn, Stuart S; Tian, Shaomin; Blake, Steven et al. (2012) Reductively responsive siRNA-conjugated hydrogel nanoparticles for gene silencing. J Am Chem Soc 134:7423-30