Large Volume Intratumoral Injection Device for Therapeutic Liver Infusions

 描述(由申请人提供)：本提案的目的是证明一种创新的注射装置(建议的产品)的可行性，以改善与目前使用的标准注射针头相比，肿瘤内肝脏疗法的输送。随着多种疾病引起的肝硬变在普通人群中的发病率增加，肝细胞癌在未来几年将成为经济资源的越来越大的负担。移植和手术治疗已经确立，并为符合条件的患者提供了令人满意的总体生存，但只有一小部分肝细胞癌患者有资格接受这些治疗。因此，相当大的努力被用于开发替代的微创治疗方法。通过直接注射的方式提供肝癌治疗，有可能显著降低目前或正在开发的治疗方法的费用和发病率。尽管直接注射是解决这一问题的一种看似简单的方法，但注射直径大于3厘米的肿瘤的能力有限，以及注射后治疗药物的分布不均匀，是直接注射的重大缺点。与传统的注射针相比，所提出的注射装置沿目标解剖的整个长度是多孔的；因此，与输液液接触的组织的表面积显著增加。假设：改进的输液输送将导致输液在肿瘤组织中更大的面积和更均匀的分布，并有助于增强各种化疗和抗肿瘤输液的治疗直接瘤内注射方案。初步数据：我们已经证明，多孔性注射设备显著改善了乙醇在正常犬前列腺中的体内分布，其他研究也证明了申请人的多孔性注射设备的独特性能优势。具体目的：该项目需要对多孔注射设备进行临床前测试，以最终应用于人类肝内肿瘤患者。目的1.证明与标准针头相比，多孔注射装置提供了更广泛的输液分布。任务1-VX-2细胞在兔体内的转移和肿瘤的生长，用于移植肿瘤组织。任务2-确定兔肝脏VX-2肿瘤内输液的最佳流量任务3-用多孔器和标准针输注VX-2肿瘤后输液成分的浓度和分布的比较。里程碑：与针头注射相比，多孔注射装置的分布将增加50%。

 DESCRIPTION (provided by applicant): The objective of this proposal is to demonstrate the feasibility of an innovative injection device (proposed product) to improve upon intratumoral delivery of liver therapeutics as compared to standard injection needles currently used. Hepatocelluar carcinoma (HCC) will become an increasing burden on economic resources in the coming years as the prevalence of cirrhosis due to multiple disease processes in the general population increases. Transplant and surgical treatment are well established and have provided satisfactory overall survival for eligible patients, however only a small minority of HCC patients are eligible for these therapies. Therefore considerable efforts have been directed toward developing alternative minimally invasive treatments. HCC therapeutic delivery by direct injection has the potential to significantly reduce the expense and morbidity of current therapeutics or those in development. Though direct injection is a seemingly straightforward approach to the problem, limited ability to inject tumors greater than 3cm in diameter and uneven distribution of the therapeutic after injection, are significant drawbacks to direct injectin. In contrast to conventional injection needles, the proposed injection device is porous along the entire length of the targeted anatomy; therefore, the surface area of tissue in contact with infusate is considerably increased. Hypothesis: Improved infusate delivery will lead to a larger area and more uniform distribution of infusate within the tumor tissue and lend itself to enhanced therapeutic direct intratumoral injection protocols for various chemoablative and anti- neoplastic infusates. Preliminary Data: We have demonstrated that porous injection devices have significantly improved in vivo distribution of ethanol within normal canine prostates and other studies have demonstrated the unique performance benefits of applicant's porous injection device. Specific Aim: This project entails preclinical testing of the porous injection device for eventual application to human patients with intrahepatic tumors. Aim 1. Demonstrate that the porous injection device provides broader distribution of an infusate compared to a standard needle. Task 1 - Transfer of VX-2 Cells and growth of tumor in rabbit for tumor implant tissue. Task 2 - Determine the preferred flow rate for infusate into the VX-2 tumor in rabbit liver Task 3 - Comparison of concentration and distribution of infusate components after infusion into VX-2 tumor with porous device and standard needle. Milestone: The porous injection device will show 50% greater distribution as compared to needle injection.