ICorps: Innovative Printing Approach for Transdermal Drug Delivery

ICorps：透皮给药的创新印刷方法

• 批准号: 1612937
• 负责人: Roger Narayan
• 金额: $ 5万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1612937&HistoricalAwards=false
• 关键词: ICorps; Innovative; Printing; Approach; Transdermal

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.

基底细胞癌是一种医学病症，其中皮肤基底层中的细胞表现出不受控制的生长。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，手术可能导致毁容疤痕。此外，完全手术切除大脑或眼睛附近的基底细胞癌肿瘤可能难以实现。最近已经开发了几种非手术基底细胞癌疗法;然而，这些治疗与许多副作用（例如，炎症和糜烂）。将抗基底细胞癌疗法直接（局部）施用至癌组织提供了优于口服或静脉内施用抗基底细胞癌疗法的几个优点，包括将高浓度的治疗剂递送至癌组织的部位。毒性作用和其他副作用可以通过使整个身体暴露于抗基底细胞癌治疗而减少。此外，精确拟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药物，该药物作为抗基底细胞癌治疗显示出巨大的前景，以克服与基底细胞癌常规治疗相关的局限性。这个I-Corps团队将使用台式研究来证明微结构设备表现出适当的皮肤相互作用和抗基底细胞癌特性，用于基底细胞癌的局部治疗。 这个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，用于基底细胞癌的局部治疗。将根据预定的临床相关里程碑比较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。具有蚊子般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。压电喷墨印刷将用于将在水性介质中显示出较差溶解性的抗基底细胞癌剂施加到微结构化医疗装置的表面。将使用称为纳米压痕的仪器压痕方法来确认微结构医疗器械的机械性能适合与肿瘤相互作用。一项涉及癌细胞和正常皮肤细胞的实验室研究将用于证实微结构医疗设备根除癌细胞，但不影响正常细胞。将使用尸体猪皮（人类皮肤的替代品）进行研究，以证实微结构医疗器械可以成功地将治疗传递到皮肤而不会断裂。该项目将支持制造用于最终人体（临床）研究的演示微结构医疗设备，从而快速开发临床使用的设备。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实验室转移到可行的商业产品中。