 |
 Return to: Department of Biomedical Engineering | UT Home |
|
People | Research | Publications | Contact Us | LabWiki | Home | |
|
Research
Our current research objectives are designed to address four areas of complexities both in applied therapeutics and in basic biomedical sciences.
Development of novel hybrid biomaterials for combinatorial delivery of drugs and genes In collaboration with Dr. L. Raja, of the Dept. of Aerospace Engineering at UT Austin, we have also developed a new surface functionalization technique for biomaterials specifically for biodegradable micro/nanoparticles. This process utilizes the newly developed atmospheric-pressure glow discharge plasma technique. Unlike conventional plasma modification of biomaterials, atmospheric–pressure glow plasma is a room temperature, atmospheric pressure phenomenon that would be highly suitable for fragile polymers and materials containing bioactive molecules that can be destroyed under harsher plasma conditions. We have successfully developed a bench top system to easily modify micro/nanoparticle surfaces for efficient loading of proteins/peptide drugs. This work has also been disclosed as an invention and a provisional patent application is being prepared by UT. In the gene therapy area we have recently developed a hybrid macromolecule by grafting the synthetic polyamines, polyethyleneimne (PEI) or polyhistidine, onto the backbone of the natural polysaccharide chitosan (invention disclosure with UT). These unique biomaterials provide us with an opportunity to combine the attributes of synthetic and natural polymers thereby creating novel entities for drug and gene delivery applications. For example, PEI grafted chitosan is a sugar-polymaine that combines both the high transfectability of PEI and the strong mucoadhesive properties of chitosan, an unique blend that could open up new directions in mucosal (oral, nasal, tracheal) delivery of genetic materials. One major motivation behind this research is the development of effective, needle-free delivery systems, which, in addition to being highly patient-compliant, could have a tremendous impact in third world countries where needle-born diseases have created devastating epidemics in recent times. Another aspect of this research has been the development of transcutaneous delivery systems for biodegradable polymer nanoparticles carrying vaccines. With the help of a grant from the National Institutes of Health (National Institute of Allergy and Infectious Diseases) we have developed a novel patch-type system for effective delivery of such particles into the immune cell-rich epidermal region of the skin. This work, recently published in the Journal of Drug delivery Sciences and Technology, was the first to demonstrate that the stratum-corneum barrier of the skin can be penetrated to deliver immune-cell targeted, biodegradable, polymer nanoparticles using optimized combinations of permeation enhancing, biocompatible chemicals. In a related effort, as part of two NIH funded projects (an R33 and a BRP grant) in collaboration with Dr. Rebecca Richards-Kortum, we are developing polymer formulations for efficient delivery of imaging contrast agents to the mucosal epithelium. Specifically we are using mucoadhesive polymers and cell permeable peptides as synthetic delivery modalities for efficient penetration and transport of gold nanoparticles and quantum dots across the cervical and oral mucosa. We are currently collaborating with clinicians and researchers at The M.D. Anderson Cancer Center at Houston and the University of Texas at Austin to develop improved DNA-based cancer and infectious diseases. In particular, we are collaborating with Dr. Larry Kwak, Chair of Lymphoma and Myeloma at the M. D. Anderson Cancer Center to develop a nucleic acid vaccine for immunotherapy against B cell lymphoma using the idiotype gene and chemokine-fusion constructs. We are also collaborating with Dr. Barry Kitto at UT Austin, in developing immunizations strategies against Rous Sarcoma Virus (RSV). These translational efforts have resulted in several grant application, specifically in the cancer immunotherapy area and pre-clinical animal trials are ongoing. References
|
Continuing on my previous research efforts during doctoral studies and subsequent
industrial experience, a major focus in the lab has been the continued development
of improved delivery strategies for nucleic acid based immunotherapeutics.
This project has both a basic research component in the development of new
materials, material modification and characterization and a strong translational
component in applying the developed strategies to pre-clinical and clinical
disease models. In the basic research area we have developed surface-functionalized,
biodegradable particles for simultaneous delivery of multiple immunotherapeutic
molecules to dendritic cells. In particular, we synthesized polyethyleneimine-grafted,
cationic microparticles for surface loading of DNA. These micro and nanoparticles
can efficiently deliver DNA-based immunotherapeutics to antigen presenting
cells while carrying immunostimulatory molecules either within the particles
or exogenously in injectable, degradable, in-situ forming hydrogels. This work
has been accepted for publication in the journal “Biomaterials” and
shows the feasibility of covalent conjugation of polyamines on the surface
of polymer microparticles and their ability to enhance gene delivery to immune
cells. An invention disclosure has been filed involving combinatorial delivery
of multiple biomolecules in a single formulation. Sudhir Kasturi, the graduate
student involved in this research also presented this as a business proposal
in the I2P (Idea to Product) competition at UT Austin and won the 3 rd prize. |
|