SBIR Phase II: Biomaterials and Chemistry to Enhance the Delivery of Medicines in the Body

这个小企业创新研究（SBIR）第二阶段项目支持开发一种技术，以改善药物在体内的输送方式。任何药物的剂量只有不到2%的剂量到达身体需要的地方。另外98%的药物要么被消除，要么更糟的是，集中在可能导致副作用的领域。从日常抗炎药到最新的癌症疗法，所有药物都会发生这种情况。如果成功的话，这种新方法将把一种常规药物变成一种药物，这种药物只在需要的地方被浓缩和激活。这一进展应该会增加治疗的有效性，并尽量减少其副作用。例如，局部药物活化可以以最小的副作用将化疗靶向肿瘤。抗生素可以以比目前更高的局部剂量输送，消除局部感染并限制耐药细菌的产生。抗炎药物可能更强大，改善术后疼痛的管理，可能减少阿片类药物的使用和滥用。总的来说，这项技术可以减少药物不良事件的昂贵负担，估计超过1770亿美元。为了创造靶向药物，研究人员依靠患病组织和身体其他部分之间的内源性差异（例如，分子标记或酶活性的差异）。局部药物活化为创造靶向药物提供了新的途径。该方法首先在所需部位注射可生物降解的聚合物。该材料含有体内其他任何地方都不存在的外源性化学活化剂。然后全身给予一种药物，该药物在与凝胶接触之前是无活性的，从而提高局部疗效并减少全身副作用。第一阶段的结果表明，灭活化疗在治疗10天后消除了小鼠的肿瘤，副作用最小。二期项目将把本地药物激活平台的益处扩展到其他疗法，包括癌症疗法和止痛药。长期目标是显示该方法对多种药物的适用性，并增加其改善影响身体局部区域的疾病结果的潜力。如果成功的话，这一进展将使那些过于虚弱而无法接受药物治疗的人能够接受药物治疗，并使治疗能够在以前由于剂量限制性毒性而不可能的组合中发挥作用。

This Small Business Innovation Research (SBIR) Phase II project supports the development of a technology to improve the way drugs are delivered in the body. Less than 2% of the dose of any medication finds its way to the place in the body where it is needed. The other 98% is either eliminated or, even worse, concentrates in areas where they can lead to side effects. This happens with all medications from daily anti-inflammatory drugs to the latest cancer therapies. If successful, this new approach will turn a regular drug into a medicine that is concentrated and activated only at the area where it is needed. This advance should increase the efficacy of the therapy and minimize its side effects. For example, the local drug activation can target chemotherapies to tumors with minimal side effects. Antibiotics could be delivered at higher local doses than is currently possible, eliminating local infections and limiting the creation of drug-resistant bacteria. Anti-inflammatory medications could be more powerful, improving the management of post-operative pain, potentially reducing the use and misuse of opioid drugs. Overall, this technology could reduce the costly burden of adverse drug events, estimated at more than $177 billion.To create targeted medicines, researchers rely on the endogenous differences between diseased tissue and the rest of the body (e.g., molecular markers or differences in enzymatic activity). Local drug activation provides a new path to create targeted medicines. The approach starts by injecting a biodegradable polymer at the desired site. The material contains exogenous chemical activators that do not exist anywhere else in the body. Then a drug is given systemically that is inactive until it comes in contact with the gel improving local efficacy and diminishing systemic side effects. Phase 1 results showed that an inactivated chemotherapy eliminated tumors in mice after only 10 days of therapy with minimal side effects. The Phase II project will expand the benefits of the local drug activation platform to other therapies, including cancer therapies and pain medications. The long-term goal is to show the applicability of the approach to multiple classes of drugs and increase their potential to improve outcomes for diseases that affect local areas of the body. If successful, this advance should enable medications for people who are too frail to receive them and enable therapies to work in combinations that were previously impossible due to dose-limiting toxicities.