Dept. of Pharmaceutics
Univ. of Minnesota
308 Harvard St. SE
Room 9-177 WDH
Minneapolis, MN 55455
Ronald A. Siegel, Sc.D.
B.S., Mathematics, 1975
University of Oregon-Eugene
Electrical Engineering and Computer Science
Massachusetts Institute of Technology
Professor Siegel's research interests lie in drug delivery systems, focusing on novel methods for achieving spatiotemporal control of drug release. Three projects are underway.
In the first project, a micromachined valve is being constructed that will provide glucose-sensitive control of insulin delivery. An integral feature of this valve is a polymer microgel that binds glucose and, as a result, changes its degree of swelling. This microgel is embedded inside a silicon microchip into which microfluidic channels have been machined. The gel's glucose-sensitive swelling and deswelling is harnessed to open or close channels through which an insulin solution flows. The result of this project, which lies at the interface between drug delivery, polymer science, and microfluidics, will be an "artificial pancreas" which delivers insulin to counteract rises in blood glucose and will be used to treat Type I diabetes.
In the second project, an implantable device is being developed that delivers hormones in rhythmic pulses. Such a device will be particularly useful in the treatment of reproductive disorders that stem from the failure of the hypothalamus to secrete gonadotropin releasing hormone in its normal rhythmic pattern. The proposed device includes a hydrophobic, polyelectrolyte hydrogel that pulsates (i.e., changes its swelling state) in the presence of glucose. Rhythmic pulsations are due to mutual feedback between the transport of blood glucose through the hydrogel and the enzyme glucose oxidase, which converts glucose to acidic hydrogen ions, which in turn alters degree of swelling and hence the rate of glucose transport through the gel. Swelling pulsations enable modulation of hormone release rates.
In a third project, a microfluidic point-of-administration mixing system is being developed for nasal delivery of diazepam, a drug that is effective in the prevention and control of epileptic seizures. In this project, a combination of thermodynamics, fluid mechanics, and microfabrication is brought to bear on delivery of a poorly soluble drug that is difficult to administer nasally.
R.A. Siegel. Oscillatory Systems Created with Polymer Membranes, in Nonlinear Dynamics with Polymers (J. Pojman and T-Q. Miyata, eds.), Wiley-VCH, Weinheim, pp 189-217 (2010).
R.A. Siegel, Y. Gu, M. Lei, A. Baldi, E.E. Nuxoll and B. Ziaie. Hard and Soft Micro- and Nanofabrication: An Integrated Approach to Hydrogel Based Biosensing and Drug Delivery. J. Controlled Release 141, 303-313 (2010).
T. Vermonden, S.S. Jena, D. Barriet, R. Censi, J. van der Gucht, W.E. Hennink and R.A. Siegel. Macromolecular Diffusion in Self-Assembling Biodegradable Thermosensitive Hydrogels. Macromolecules 43, 782-789 (2010).
E.E. Nuxoll, M.A. Hillmyer, R. Wang, C. Leighton and R.A. Siegel. Composite Block Polymer-Microfabricated Silicon Nanoporous Membrane. ACS Appl. Mater. Interf. 1, 888-893 (2009).
V.D. Ivaturi, J.R. Riss, R.L. Kriel, R.A. Siegel and J.C. Cloyd. Bioavailability and Tolerability of Intranasal Diazepam in Healthy Adult Volunteers. Epilepsy Research 84, 120-126 (2009).
D.F. Bayramov, P. Singh, G.W. Cleary, R.A. Siegel, A.E. Chalykh and M.M. Feldstein. Noncovalently Crosslinked Hydrogels Displaying a Unique Combination of Water Absorbing, Elastic and Adhesive Properties. Polym. Int. 57, 785-790 (2008).
S.K. Mujumdar, A.S. Bhalla and R.A. Siegel. Novel Hydrogels for Rhythmic Pulsatile Drug Delivery. Macromol. Symp. 254, 338-344 (2007).
M. Lei, B. Ziaie, E. Nuxoll, K. Ivan, Z. Noszticzius and R.A. Siegel. Integration of Hydrogels with Hard and Soft Microstructures. J. Nanosci. Nanotech. 7, 780-789 (2007).
H. Hou and R.A. Siegel. Enhanced Permeation of Diazepam through Artificial Membranes from Supersaturated Solutions. J. Pharm. Sci. 95, 896-905 (2006).
M. Lei, A. Baldi, E. Nuxoll, R.A. Siegel and B. Ziaie. A Hydrogel-Based Implantable Micromachined Transponder for Wireless Glucose Measurement. Diabetes Tech. Therap. 8, 112-122 (2006).
B. Ziaie, A. Baldi, M. Lei, Y. Gu and R.A. Siegel. Hard and Soft Micromachining for BioMEMS: Review of Techniques and Examples of Applications in Microfluidics and Drug Delivery. Adv. Drug Deliv. Revs. 56, 145-172 (2004).
G.P. Misra and R.A. Siegel. A New Mode of Drug Delivery: Long-Term Autonomous Rhythmic Hormone Release Across a Hydrogel Membrane. J. Controlled Release 81, 1-6 (2002).