Our current research objectives are designed to address four areas of complexities both in applied therapeutics and in basic biomedical sciences.

• Development of micro-fabricated polymer structures with pre-designed spatio-temporal patterning of bio-factors to study stem cell differentiation
• Studying stem and progenitor cell behavior in 3D environments and developing new approaches for high-throughput production of therapeutic cells
• Development of novel hybrid biomaterials for combinatorial delivery of drugs and genes
• Design and development of BioMEMS-based, injectable devices for physiologically-controlled drug delivery and simultaneous therapeutic imaging

Design and development of BioMEMS-based, injectable devices for sensor-controlled drug delivery and simultaneous therapeutic imaging

A related area of focus in drug delivery has been our effort in developing micro/nano fabricated devices for physiologically-responsive delivery of chemotherapeutic agents and imaging molecules to tumor tissues. As a member of the NSF-IGERT program in diagnostic and therapeutic imaging at The University of Texas, my major interest in this area is to combine smart polymeric membranes and top-down nanofabrication techniques for on-demand, disease-triggered drug delivery and imaging for therapeutic monitoring within the same platform.

The field of drug and gene delivery, till now, has primarily focused on bottom-up design approaches (self-assembly, polymer particles, hydrogels etc.) that are diffusion/degradation controlled and rarely incorporates physiological responsiveness. In recent years few researchers have reported top-down manufacturing approaches to create microfabricated delivery platforms (drug microchips, microfabricated oral delivery particles etc.) with multiple functionality and predictable, triggered release of drugs. However, these top-down efforts are yet to achieve true nano-scale structures and physiological responsiveness, achievements that could truly revolutionize drug delivery and therapeutic imaging by creating “injectable” BioMEMS structures capable of sensor-controlled delivery of drugs and genes and simultaneously allowing for high-resolution, real-time imaging of the target organ.

Our goal is to combine the bottom-up and top-down approach in a single platform to fabricate <500nm size injectable drug reservoirs that could release drugs inside a target cell when, and only when, triggered by a specific physiological stimulus. Simultaneously, the design would allow for monitoring the drug release profile and tissue distribution of the MEMS particles using non-invasive imaging techniques. On-demand, physiologically-triggered drug release in-vivo could allow for novel therapeutic strategies for cancer and other diseases with significantly lower systemic toxicity along with continual monitoring of therapy.

With the help of start-up funding from the Tate foundation (UT Austin, Texas CBME Biomedical Research Grant) we have developed E-beam based templates for thermal nanoimprinting and step and flash nanoimprint lithography and demonstrated, for the first time, that drug delivery containers can be fabricated at the 200 nm length scale using a purely top down approach. We have also developed enzyme-responsive polymer membranes to serve as a “lid” for these delivery devices resulting in truly stimuli-responsive drug nanocontainers. We have submitted an invention disclosure that is currently being converted to a provisional patent application by UT. In addition, we have recently submitted an NIH R01 proposal as one of six proposals for a Cancer Center for Nanotechnology Excellence (CCME) U54 grant application in collaboration with M.D. Anderson Cancer Center, Rice University and UT Austin. Specifically, in collaboration with Dr. Jack Roth, Chief of Thoracic Surgery at the M. D. Anderson Cancer Center, we would use such nanofabricated devices for delivering a newly developed, apoptotic peptide drug for the treatment of non small-cell lung cancers.