ICorps: Innovative Printing Approach for Transdermal Drug Delivery

基底细胞癌是一种皮肤基底层细胞生长不受控制的医学疾病。2010年，近300万美国人被诊断患有基底细胞癌，这是西班牙裔和高加索人中最常见的癌症。这种情况通常通过手术切除受影响的皮肤来治疗。不幸的是，手术会导致毁容的疤痕。此外，完全手术切除靠近大脑或眼睛的基底细胞癌可能很难实现。最近发展了几种非手术基底细胞癌治疗方法；然而，这些治疗有许多副作用（如炎症和糜烂）。与口服或静脉注射抗基底细胞癌治疗相比，将抗基底细胞癌治疗直接（局部）施用于癌组织提供了若干优点，包括将高浓度治疗剂输送到癌组织部位。通过尽量减少全身暴露于抗基底细胞癌治疗中，可以减少毒性作用和其他副作用。此外，精确符合基底细胞癌肿瘤几何形状的治疗可能比基于任意肿瘤尺寸的治疗更有效。该项目将应用基于喷墨打印的增材制造技术和一种具有巨大前景的抗基底细胞癌治疗药物，以克服与传统基底细胞癌治疗相关的局限性。这个I-Corps团队将使用台式研究来证明微结构装置在局部治疗基底细胞癌时表现出适当的皮肤相互作用和抗基底细胞癌特性。I-Corps项目的目标是使用基于喷墨打印的增材制造方法来制备具有仿生设计的微结构设备，用于局部治疗基底细胞癌。机械性能和功能参数，包括医疗器械材料的刚度、器械材料的抗癌活性、器械的断裂性能和器械的皮肤相互作用性能，将与预定的临床相关里程碑进行比较。具有类似蚊子仿生设计的微结构医疗设备将使用基于光聚合的增材制造和微成型的组合来制备。压电喷墨打印将用于将抗基底细胞癌剂应用于微结构医疗设备的表面，该剂在水介质中溶解性差。将使用一种称为纳米压痕的仪器压痕方法来确认微结构医疗设备的机械性能是否适合与肿瘤相互作用。一项涉及癌细胞和正常皮肤细胞的台式研究将被用来证实这种微结构医疗设备能根除癌细胞，而不影响正常细胞。用猪尸体皮（人类皮肤的替代品）进行的研究将证实微结构医疗设备可以成功地将治疗传递到皮肤而不会骨折。该项目将支持最终用于人体（临床）研究的示范性微结构医疗设备的制造，从而导致临床使用设备的快速发展。此外，I-Corps项目将评估如何将这种创新的抗基底细胞癌疗法从台式转化为可行的商业产品。

Basal cell carcinoma is a medical condition in which the cells in the basal layer of the skin exhibit uncontrolled growth. In 2010, nearly three million Americans were diagnosed with basal cell carcinoma, which the most common cancer among Hispanics and Caucasians. This condition is commonly treated by surgical removal of the affected skin. Unfortunately, surgery can lead to disfiguring scarring. In addition, complete surgical removal of basal cell carcinoma tumors near the brain or the eyes may be difficult to achieve. Several non-surgical basal cell carcinoma therapies have been recently developed; however, these treatments are associated with many side effects (e.g., inflammation and erosion). Direct (topical) administration of an anti-basal cell carcinoma therapy to the cancerous tissue provides several advantages over either oral or intravenous administration of an anti-basal cell carcinoma therapy, including delivery of a high concentration of the therapeutic agent to the site of the cancerous tissue. Toxic effects and other side effects may be reduced by minimizing exposure of the entire body to the anti-basal cell carcinoma therapy. In addition, treatments that precisely fit the geometry of the basal cell carcinoma tumor may be more effective than treatments that are based on arbitrary tumor dimensions. This project will apply inkjet printing-based additive manufacturing technology and a drug that shows tremendous promise as an anti-basal cell carcinoma therapy to overcome limitations associated with conventional treatment of basal cell carcinoma. This I-Corps team will use benchtop studies to demonstrate that the microstructured devices exhibit appropriate skin interaction and anti-basal cell carcinoma properties for topical treatment of basal cell carcinoma. The goal of this I-Corps project is to use an inkjet printing-based additive manufacturing approach to prepare microstructured devices with a biomimetic design for localized treatment of basal cell carcinoma. The mechanical properties and functionality parameters, including the stiffness of the medical device material, the anti-cancer activity of the device material, the fracture properties of the device, and the skin interaction properties of the device, will be compared against predetermined clinically-relevant milestones. Microstructured medical devices with a mosquito-like biomimetic design will be prepared using a combination of photopolymerization-based additive manufacturing and micromolding. Piezoelectric inkjet printing will be used to apply an anti-basal cell carcinoma agent that shows poor solubility in aqueous media to the surfaces of the microstructured medical devices. An instrumented indentation approach known as nanoindentation will be used to confirm that the mechanical properties of the microstructured medical device are appropriate for interaction with the tumor. A benchtop study involving cancerous and normal skin cells will be used to confirm that the microstructured medical device eradicates cancerous cells but leaves normal cells unaffected. Studies with cadaveric porcine skin, a substitute for human skin, will be used to confirm that microstructured medical device can successfully deliver the therapy to the skin without fracture. This project will support the fabrication of demonstrator microstructured medical devices for eventual human (clinical) studies, leading to the rapid development of devices for clinical use. In addition, the I-Corps project will assess how to transfer this innovative anti-basal cell carcinoma therapy from the benchtop into a viable commercial product.