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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
Application #
Study Section
Special Emphasis Panel ()
Program Officer
Fu, Yali
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Schools of Arts and Sciences
Chapel Hill
United States
Zip Code
Khodabandehlou, Khosrow; Tian, Shaomin; Luft, James C et al. (2016) Particles for Local Delivery of Proteins Using Intra-Articular Route. Adv Healthc Mater 5:653-8, 626
Roberts, Reid A; Eitas, Timothy K; Byrne, James D et al. (2015) Towards programming immune tolerance through geometric manipulation of phosphatidylserine. Biomaterials 72:1-10
Mueller, Sarah N; Tian, Shaomin; DeSimone, Joseph M (2015) Rapid and Persistent Delivery of Antigen by Lymph Node Targeting PRINT Nanoparticle Vaccine Carrier To Promote Humoral Immunity. Mol Pharm 12:1356-65
Khodabandehlou, Khosrow; Kumbhar, Amar S; Habibi, Sohrab et al. (2015) Silylated precision particles for controlled release of proteins. ACS Appl Mater Interfaces 7:5756-67
Robbins, Gregory R; Roberts, Reid A; Guo, Haitao et al. (2015) Analysis of human innate immune responses to PRINT fabricated nanoparticles with cross validation using a humanized mouse model. Nanomedicine 11:589-99
Ma, Da; Tian, Shaomin; Baryza, Jeremy et al. (2015) Reductively Responsive Hydrogel Nanoparticles with Uniform Size, Shape, and Tunable Composition for Systemic siRNA Delivery in Vivo. Mol Pharm 12:3518-3526
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
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
Hasan, Warefta; Chu, Kevin; Gullapalli, Anuradha et al. (2012) Delivery of multiple siRNAs using lipid-coated PLGA nanoparticles for treatment of prostate cancer. Nano Lett 12:287-92
Kersey, Farrell R; Merkel, Timothy J; Perry, Jillian L et al. (2012) Effect of aspect ratio and deformability on nanoparticle extravasation through nanopores. Langmuir 28:8773-81

Showing the most recent 10 out of 17 publications