Jason William Castle

Ultrasound-mediated targeted drug delivery: recent success and remaining challenges

The potential clinical value of developing a novel, nonviral, ultrasound-directed gene and drug delivery system is immense. Investigators soon will initiate clinical trials with the goal of treating a wide variety of maladies using noninvasive, ultrasound-based technology. The ongoing, scientific validation associated with promising preclinical success portents a novel range of therapeutics. The clinical utility and eventual clinical successes await vigorous testing. This review highlights the recent successes and challenges within the field of ultrasound-mediated drug delivery.

Drug and Gene Delivery using Sonoporation for Cardiovascular Disease

Using the improvements made in diagnostic contrast enhanced ultrasound, researchers have made significant progress in the field of ultrasound-mediated sonoporation for drug delivery. Many programs take advantage of commercial products; both ultrasound imaging systems and contrast agents to better enable translation from preclinical to first-in-man studies (Kotopoulis et al., Med Phys 40:072902, 2013). Particularly well-suited targets for this novel therapy are diseases of the cardiovascular system. This chapter will highlight several recent studies addressing treatment of both acute and chronic conditions.

Ultrasound-Directed, Site-Specific Gene Delivery

With the implementation of gene therapy looming in the near term, an effective delivery system using noninvasive, nonviral-mediated methods appears as an attractive option. This novel platform technology uses gas-filled, ultrasound-directed acoustic microspheres for both diagnostic imaging and therapy and yet may provide a key component for future success in the pursuit of single-gene replacement therapy.

Optison™ Albumin Microspheres in Ultrasound-Assisted Gene Therapy and Drug Delivery

Optison™ (Perflutren Protein-Type A Microspheres Injectable Suspension, USP) is a sterile non-pyrogenic suspension of microspheres of human serum albumin with perflutren (also known as perfluoropropane). Optison™ microspheres are micrometre-sized gas-filled bubbles that have a shell consisting of human albumin. The size range is 2–4 μm in diameter and 95 % are less than 10 μm. This means that intravenously injected Optison™ may pass through the pulmonary capillary bed and access all parts of the systemic vasculature. The size distribution, shell properties and gas core provide a bubble that oscillates in response to and scatters ultrasound at frequencies useful for clinical imaging. The established use of Optison™ is in the field of echocardiography, where it provides echogenic contrast enhancement for suboptimal echocardiograms.

Pilot study assessing the impact of platelet activation electric stimulation protocols on hematopoietic and mesenchymal stem cell proliferation

Recent research has shown that pulsed electric fields can successfully activate platelets ex-vivo; activation means here the release of growth factors and clotting. Typically, platelets are in a complex biological matrix, such as platelet rich plasma (PRP), which contains a variety of cell types. While specific electric pulses can activate the platelets, the impact of electric simulation on other cell types is an open question. The pilot study presented here focuses on evaluating electric pulse effects on hematopoietic and mesenchymal stem cells when they are in a complex biological matrix also containing platelets. Experimental results indicate that stem cell proliferation at two weeks post treatment can be tuned as a function of electrical parameters. We demonstrate in this pilot study that stem cell proliferation can be either low (via conductive coupling, 8.5 kV/cm electric field amplitude) or high (via capacitive coupling, 2.5 kV/cm electric field amplitude) two weeks after stimulation, despite these two electric pulse delivery mechanisms inducing roughly similar growth factor release and immediate cell viability post treatment. These observations may open up additional ways of tuning electric pulse delivery for platelet activation and other biomedical applications.