Projects

Recombinant Polymers for Localized Drug Delivery and as Liquid Embolics

Polymers produced by recombinant techniques provide exquisite control over monomer sequence and polymer length. Such control enables systematic correlation of structure with function in the context of drug and gene delivery. Our group has extensively studied recombinant silk-elastinlike protein polymers (SELPs) for matrix-mediated delivery of bioactive agents to solid tumors. We have investigated the influence of polymer structure on gel network formation, mechanical properties, bioactive agent release, degradation, spatial and temporal control over transfection, and safety and efficacy in head and neck cancer models. More recent work involves the use of SELPs as liquid embolics for the treatment of hepatocellular carcinoma and cerebral aneurysms, as well as for delivery of glycosaminoglycans in the treatment of radiation-induced proctitis and inflammatory conditions.

Biological Fate and Biocompatibility of Silica Based Nanoconstructs

Recent advances in nanotechnology have enabled the fabrication of inorganic nanoconstructs with defined shape, size, and surface functionality. Such particles have been used for imaging and delivery in diagnosis and/or treatment of a number of diseases. Little is known about the influence of such physicochemical properties on toxicity. Our research group studies the influence of size, charge, surface properties, geometry and porosity of silica nanoparticles on their cellular uptake, biodistribution, toxicity and immune response.

Controlled Drug Delivery in Chronic Rhinosinusitis (CRS)

Chronic rhinosinusitis (CRS) is a debilitating disease secondary to the underlying chronic inflammatory immune dysfunction that substantially diminishes the quality of life and productivity. Current available therapies are inadequate to alleviate the symptoms of patients who undergo surgical management every year, underscoring the dire need for new therapeutic strategies. Vascular permeability of inflamed sinonasal tissue enables the accumulation and retention of systemically delivered nanoscale liposomal carriers within the inflamed sinonasal tissue. In collaboration with the Department of Otolaryngology, we are investigating delivery approaches for more effective and less toxic treatment of CRS.

Water-Soluble Polymer-Drug Conjugates for Targeted Delivery of Bioactive Agents

Targeted delivery of bioactive agents by water soluble polymers can increase efficacy and reduce toxicity. We have investigated the synthesis, characterization and biological evaluation of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-peptide conjugates for targeted delivery of drugs and radionuclides to solid tumors. The influence of local hyperthermia on improved delivery of such conjugates has been investigated. More recent work involves targeting the tumor extracellular matrix by modifying the side chains with collagen mimetic peptides.

Reducing Drug Adsorption in Extracorporeal Membrane Oxygenator (ECMO) Systems

Extracorporeal Membrane Oxygenation (ECMO) system is a life-saving cardiopulmonary bypass device used in critically ill patients with refractory heart and lung failure. Patients supported with ECMO receive numerous drugs to treat critical illnesses. Unfortunately, the majority of drugs prescribed to patients on ECMO lack dosing information. Preliminary data demonstrates that dosing is different in this population because the ECMO circuit components can adsorb drugs and affect drug exposure substantially. In collaboration with the Division of Clinical Pharmacology, Department of Pediatrics of The University of Utah, we are investigating drug modification strategies to reduce their adsorption to the ECMO circuits.

Improving Surgical Outcomes in Oropharyngeal Squamous Cell Carcinoma

The prevalence of human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinomas (OPSCCa) has been rising at an alarming rate. Although surgical management with transoral robotic surgery (TORS) improves treatment outcomes, with reduced morbidity and positive surgical margins, tumor recurrence rates remain high. Preliminary data demonstrate the feasibility of employing fluorescent image (FI)-guided TORS with indocyanine green (ICG) for HPV+ OPSCCa treatment. In collaboration with the Department of Otolaryngology, we are investigating strategies to improve surgical outcomes in OPSCCa patients by both passive targeting (EPR effect) and active targeting (targeting vascular dysregulation).