(G-247) A thermally responsive liposome drug delivery system for in-vivo targeting for ulcerative colitis

Ulcerative colitis, an inflammatory bowel disease (IBD) that causes intestinal inflammation, presents a challenge in terms of treatment options. Currently, patients have limited choices, including oral medications, surgery, or supportive care. These therapeutics include medications that target the colon, specific areas of the bowel, immune response repressors, along with more biologic agents, which are administered systemically or parenterally. Side effects of these therapeutics include fever, rash, itching, blistering skin, mouth sores, swelling of the eyes, and much more. Thus, there is a pressing clinical need for a treatment that is less invasive, less toxic, and more localized to the inflamed location.

To address this, we developed a controlled release platform that will release payload in response to temperature. These mobile microrobots are capable of movement in-vivo. The microrobot is loaded with a thermally responsive drug payload, which is activated via ultrasound-induced heating. This heating allows for a localized drug release using heat sensitive lipid nanoparticles. In order to achieve the first part of this process, which is a focused ultrasound system to generate ultrasound-induced heating, tissue-mimicking phantoms were created using agarose and water. These phantoms were then warmed and maintained at 37°C, while a petri dish filled with water was also kept at 37°C to ensure that the phantoms were at physiologically relevant temperatures (Figure 1).

We used an infrared thermal imaging camera to measure and analyze the temperature changes before and after using the focused ultrasound system. Through an initial optimization study, optimal settings for the focused ultrasound system were determined. This involved utilizing 7W of power, 1ms period, 0.2ms burst length, at 180s of time total. With a starting temperature of 37-38°C, the ending temperature after using the focused ultrasound system was measured at 42-43°C, suggesting a consistent change in temperature of about 5°C (Figure 2, Figure 3). This target temperature range aligns with the melting temperature of the selected thermally responsive lipids (41°C). These lipids will be used to create lipid nanoparticles, which when heated to 41°C, will break down to release the drug payload. Moving forward, we aim to demonstrate the localized heating capabilities of the focused ultrasound system. To do so, the standard ultrasound system will be used to image the entire phantom while the focused ultrasound system will be used on the side to melt the phantom and ensure that it solely affects the region of interest within tissue.