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疾病，其中皮肤基底层中的细胞表现出不受控制的生长。 2010年，将近300万美国人被诊断出患有基底细胞癌，这是西班牙裔和高加索人中最常见的癌症。这种情况通常是通过手术去除受影响的皮肤来治疗的。不幸的是，手术会导致畸形疤痕。此外，可能难以实现大脑附近的基底细胞癌肿瘤的完全外科手术去除。最近已经开发了几种非手术基底细胞癌疗法。但是，这些治疗与许多副作用有关（例如炎症和侵蚀）。直接（局部）给癌组织的抗基质细胞癌治疗提供了比口服或静脉注射抗基质细胞癌疗法的几个优势，包括将高浓度的治疗剂递送到癌组织的部位。通过最大程度地减少整个身体暴露于抗基质细胞癌治疗，可以降低毒性作用和其他副作用。此外，精确符合基底细胞癌的几何形状的治疗可能比基于任意肿瘤维度的处理更有效。该项目将采用基于喷墨印刷的添加剂制造技术和一种药物，该药物表现出巨大的希望作为一种抗基础细胞癌疗法，以克服与基础细胞癌的常规治疗相关的局限性。该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巴萨细胞癌特性，用于基础细胞癌的局部治疗。 这个I-Corps项目的目的是使用基于喷墨印刷的添加剂制造方法来制备具有仿生设计的微结构设备，用于基础细胞癌的局部处理。将与预先确定的临床上相关的里程碑进行比较，将机械性能和功能参数（包括医疗设备材料的刚度，设备材料的抗癌活性，设备的断裂特性以及设备的皮肤相互作用特性）进行比较。具有蚊子样仿生设计的微结构医疗设备将使用基于光聚合化的添加剂制造和微塑料的组合来制备。压电喷墨打印将用于应用抗基质细胞癌剂，该抗基细胞癌剂在水性培养基中对微结构医疗设备表面的溶解度差。一种称为纳米识别的仪器凹痕方法将用于确认微结构医疗设备的机械性能适用于与肿瘤的相互作用。一项涉及癌细胞和正常皮细胞的台式研究将用于确认微结构医疗器械消除了癌细胞，但会使正常细胞不受影响。尸体猪皮肤是人类皮肤的替代品的研究，将用于确认微结构的医疗装置可以成功地将治疗方法用于皮肤而不会骨折。该项目将支持示威者微观结构的医疗设备，以进行最终的人（临床）研究，从而迅速开发用于临床使用的设备。此外，I-Corps项目将评估如何将这种创新的抗基础细胞癌疗法从台式转移到可行的商业产品中。