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 endosco

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
5DP1OD006432-02
Application #
7939796
Study Section
Special Emphasis Panel (ZGM1-NDPA-B (02))
Program Officer
Jones, Warren
Project Start
2009-09-30
Project End
2014-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
2
Fiscal Year
2010
Total Cost
$740,000
Indirect Cost
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
Kai, Marc P; Brighton, Hailey E; Fromen, Catherine A et al. (2016) Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance. ACS Nano 10:861-70
DeSimone, Joseph M; Mecham, Sue J; Farrell, Crista L (2016) Organic Polymer Chemistry in the Context of Novel Processes. ACS Cent Sci 2:588-597
Fromen, Catherine A; Rahhal, Tojan B; Robbins, Gregory R et al. (2016) Nanoparticle surface charge impacts distribution, uptake and lymph node trafficking by pulmonary antigen-presenting cells. Nanomedicine 12:677-687
Roode, Luke E; Brighton, Hailey; Bo, Tao et al. (2016) Subtumoral analysis of PRINT nanoparticle distribution reveals targeting variation based on cellular and particle properties. Nanomedicine 12:1053-1062
Fromen, Catherine A; Robbins, Gregory R; Shen, Tammy W et al. (2015) Controlled analysis of nanoparticle charge on mucosal and systemic antibody responses following pulmonary immunization. Proc Natl Acad Sci U S A 112:488-93
Shen, Tammy W; Fromen, Catherine A; Kai, Marc P et al. (2015) Distribution and Cellular Uptake of PEGylated Polymeric Particles in the Lung Towards Cell-Specific Targeted Delivery. Pharm Res 32:3248-60
Byrne, James D; Jajja, Mohammad R N; O'Neill, Adrian T et al. (2015) Local iontophoretic administration of cytotoxic therapies to solid tumors. Sci Transl Med 7:273ra14
Xu, Jing; Wong, Dominica H C; Byrne, James D et al. (2013) Future of the particle replication in nonwetting templates (PRINT) technology. Angew Chem Int Ed Engl 52:6580-9
Xu, Jing; Luft, J Christopher; Yi, Xianwen et al. (2013) RNA replicon delivery via lipid-complexed PRINT protein particles. Mol Pharm 10:3366-74
Moga, Katherine A; Bickford, Lissett R; Geil, Robert D et al. (2013) Rapidly-dissolvable microneedle patches via a highly scalable and reproducible soft lithography approach. Adv Mater 25:5060-6

Showing the most recent 10 out of 19 publications