Vesna Zderic

Enhanced Ocular Drug Delivery
Our objective has been to determine combinations of ultrasound parameters that can provide optimal delivery of different drugs into the eye, study mechanisms of ultrasound action, and determine long-term safety of this application. We showed previously that exposing cornea to therapeutic ultrasound can lead to up to 10 times more delivery of a drug-mimicking compound into the eye, with only minimal alterations in the corneal structure. Subsequently, we continued to work on drug delivery problems with significant clinical relevance, such as promoting delivery of antibiotics and steroids for treatment of eye inflammations through an NIH funded project. This work indicated that ultrasound can be effective and safe for delivery of steroids into the eye in vivo. Current work focuses on modeling of temperature increases in the eye during ultrasound application, studies of the effectiveness of delivery of anti-parasitic drugs into the eye, and delivery of macromolecules via transscleral route for treatment of macular degeneration.  This work is expected to eventually lead to development of an inexpensive, quick and non-invasive ultrasound method that can be applied in an outpatient clinic to allow targeted delivery of medications into diseased eye tissues for treatment of different diseases including infections and retinopathies.

Stimulation of Insulin Release from Pancreatic Beta Cells
Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions. Pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. Thus, new modes of therapy are needed that will target directly the underlying causes of abnormal glucose metabolism. The objective of our study, funded by NIH, is to explore a novel, non-pharmacological approach that utilizes the application of ultrasound energy to safely augment insulin release from pancreatic beta cells as a potential novel treatment for type 2 diabetes.

Nail Drug Delivery
It is estimated that up to 32 million Americans are suffering from onychomycosis. This is a fungal nail disorder that is characterized by thick and yellow nails, can be extremely painful, and has also been documented to lead to many psychosocial issues. In onychomycosis, the fungus lives in the nail bed. Although there are several good antifungal drugs available for treatment, most are applied to the top of the nail and since the nail has poor permeability they do not reach the nail bed reliably and, therefore, are not very effective in treating the fungus. We have been working on the application of low intensity ultrasound to promote permeability of antifungal drugs into the nail. Our preliminary tests indicated that ultrasound increases permeability of the nail by 50% for a drug mimicking compound. In our current work, we are planning to use antifungal nail polish that is prescribed to patients suffering from onychomycosis and see the effectiveness of combining it with ultrasound excitation in order to improve permeation.  People who would benefit the most from this treatment are those in their 60s or older, particularly those who suffer from diabetes, poor circulation, immunosuppressive diseases, or have cancer that is being treated with radiation.

From 2014-2018

• Kaifi R, Price L, Chen A, Sarani B, Zderic V. Intra- and Interobserver Reliability and Variability of Femoral Artery Pseudoaneurysm Measurements Between Pre- and Postprocessed B-mode Sonographic Images. Journal of Diagnostic Medical Sonography, Dec 2018, https://doi.org/10.1177/8756479318819993.
• Kline-Schoder A, Le Z, Zderic V. Ultrasound-enhanced Drug Delivery for Treatment of Onychomycosis. J Ultrasound Med. 2018 Jul;37(7):1743-1752.
• Singh T, Suarez Castellanos I, Klimas A, Entcheva E, Cohen J, Jeremic A, Zderic V. Ultrasound-enhanced Stimulation of Insulin Release as a Potential Novel Treatment for Type 2 Diabetes. 2018 IEEE EMBS Conference Proceedings, Honolulu, 2018.
• Kline-Schoder A, Sweeney L, Le Z, Zderic V. Ultrasound-enhanced Drug Delivery for Treatment of Onychomycosis. 2018 IEEE EMBS Conference Proceedings, Honolulu, 2018.
• Suarez Castellanos I, Singh T, Balteanu B, Chatterjee Bhowmick D, Jeremic A, Zderic V. Calcium-dependent Ultrasound Stimulation of Secretory Events from Pancreatic Beta Cells. J Ther Ultrasound. 2017 Dec 5;5:30. doi: 10.1186/s40349-017-0108-9. 
• Suarez Castellanos I, Jeremic A, Cohen J, Zderic V. Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells as a Potential Novel Treatment for Type 2 Diabetes. Ultrasound Med Biol, 2017 Jun;43(6):1210-1222. doi: 10.1016/j.ultrasmedbio.2017.01.007. Epub 2017 Mar 25.
• Hariharan P, Nabili M, Guan A, Zderic V, Myers M. Model for Porosity Changes Occurring during Ultrasound-Enhanced Transcorneal Drug Delivery. Ultrasound Med Biol, 2017 Jun;43(6):1223-1236. doi: 10.1016/j.ultrasmedbio.2017.01.013. Epub 2017 Mar 21.
• Suarez Castellanos I, Balteanu B, Singh T, Zderic V.  Therapeutic Modulation of Calcium Dynamics using Ultrasound and Other Energy-based Techniques.  IEEE Reviews in Biomedical Engineering, 2016 Apr 21. doi: 10.1109/RBME.2016.2555760.
• Suarez Castellanos I, Balteanu B, Singh T, Jeremic A, Zderic V. Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells. CLAIB 2016 Latin American Congress on Biomedical Engineering, Santander, Colombia, October 2016.
• Nabili M, Geist S, Zderic V. Thermal Safety of Ultrasound-enhanced Ocular Drug Delivery: A Modeling Study. Med Phys 2015 Oct;42(10):5604. 
• Nabili M, Shenoy A, Chawla S, Mahesh S, Liu J, Geist S, Zderic V. Ultrasound-enhanced Ocular Delivery of Dexamathasone Sodium Phosphate: An In Vivo Study. J of Therapeutic Ultrasound, March 2014;2:6.  

• Reviewer for NIH IGIS Study Section, 2018 - now
• Reviewer for Focused Ultrasound Foundation, 2018 - now
• Associate Editor for IEEE EMBC meetings, 2011 - now
• Reviewer for Ultrasound Med Biol, Ultrasonics, Medical Physics, J of Hyperthermia, IEEE Transactions on Biomedical Engineering, and IEEE UFFC Transactions, 2006 - now
• Member of IEEE Engineering in Medicine and Biology Society Technical Committee on Therapeutic Systems and Technologies, 2010 - now
• Member of Advisory Editorial Board for Ultrasound in Medicine and Biology, 2011 - 2018
• Reviewer for NIH NOIT and ETTN L53 Study Sections, 2017 - 2018
• Reviewer for NIH ZRG1 SBIB Z-58 R Study Section, 2016 - 2018 
• Reviewer for NIH SPARC OT2 Study Section, 2017
• Reviewer for NIH Small Business Medical Imaging Study Section, 2010 - 2016
• Associate Editor for IEEE EMBC conferences, 2011 - 2012
• Reviewer for NIH Small Business Medical Imaging Study Section, 2010 - 2016
• Reviewer for NIH Radiation Therapeutic and Biology (RTB) study section, 2014 - 2016

Current Research Support

• NIH R21EB026152 “Low-intensity Ultrasound for Control of Cardiac Electromechanics: A Mechanistic Investigation”, Role: Multiple-PI, 2018 – 2020
• NSF I-Corps Program “Ultrasound-enhanced Drug Delivery for Treatment of Onychomycosis”, Role: PI, 2018 – 2019
• W Cross-Disciplinary Research Fund “Ultrasound-enhanced delivery of macromolecules for treatment of ocular diseases”, Role: PI, 2018 – 2019
• W University Facilitating Fund “Low-intensity Ultrasound for Control of Cardiac Electromechanics: A Mechanistic Investigation”, Role: PI, 2018 – 2019

• Patent #7,670,291. Vaezy S, Held RT, Sikdar S, Managuli R, Zderic V. Interference-Free Ultrasound Imaging During HIFU Therapy, Using Software Tools. Awarded on March 2^nd, 2010.
• Patent #8,414,494. Vaezy S, Yu J, Zderic V. Thin-profile Therapeutic Ultrasound Applicators. Awarded on April 9^th, 2013.
• Patent #8,611,189.  Vaezy S, Nguyen TN, Zderic V, Foley JL.  Acoustic Coupler using an Independent Water Pillow with Circulation for Cooling a Transducer. Awarded on December 17^th, 2013.
• Patent Application.  Ultrasound-enhanced Drug Delivery for Treatment of Onychomycosis.  Zderic V, Kline-Schoder A, Le Z. Filed in August of 2017.