A nanofluidic platform for tunable drug delivery

用于可调药物输送的纳米流体平台

• 批准号: 10093084
• 负责人: Alessandro Grattoni
• 金额: $ 33.89万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10093084
• 关键词: Address; Animal Model; Animals; Atenolol; Back; Biological; Biological Products; Biomedical Research; Blood specimen; Bluetooth; Chemical Agents; Clinic; Communication; Complex; Consumption; Development; Device Designs; Devices; Disease; Dose; Drug Delivery Systems; Drug Evaluation; Drug Formulations; Drug Kinetics; Drug Modulation; Electrodes; Electronics; Electrostatics; Enalapril; Equilibrium; Extravasation; Foreign Bodies; Formulation; Frequencies; Implant; In Vitro; Infiltration; Interruption; Intervention; Investigation; Investigational Therapies; Laboratories; Macaca; Measures; Medical; Membrane; Methotrexate; Modeling; Mus; Patients; Performance; Personal Satisfaction; Pharmaceutical Preparations; Play; Preclinical Drug Development; Process; Property; Proteins; Rattus; Regimen; Reproducibility; Research; Research Personnel; Resistance; Resources; Rodent; Safety; Schedule; System; Technology; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; Toxic effect; Validation; anti-PD-1; appropriate dose; base; biomaterial compatibility; controlled release; cost; cost effective; design; flexibility; implantable device; in vivo; in vivo evaluation; innovation; instrument; molecular size; nanochannel; nanofluidic; nanoparticle; nonhuman primate; novel therapeutics; pre-clinical research; prototype; radio frequency; remote control; research clinical testing; response; small molecule; stability testing; subcutaneous; tool; treatment duration

Every novel drug or therapeutic regimen, whether based on biological or chemical agents, requires extensive investigations for the assessment of dosing, formulation, administration schedule, and duration. These studies, however, are complex, costly and time consuming, indicating the need for a versatile and effective enabling tools to test and correct in real time for inappropriate dosing, duration, and frequency of administration. In this study, we will develop a remotely controlled implantable nanofluidic technology that enables precise increase, decrease, activation, or interruption of drug delivery in vivo. The technology is highly innovative, and offers long-term, fine, continuous modulation in dose centered on the use of embedded gate electrodes and Bluetooth Low Energy Radio Frequency (RF) communication. Further distinction is based on three key aspects: 1) electrostatic gating of nanochannels, 2) ultra-low power consumption, and 3) implant versatility with respect to drug composition (small molecules, proteins and nanoparticles can all be released), animal size (the implant is suitable for small and large animals), and material composition (inexpensive components). To develop this device, we propose the following experimental aims: Aim 1) To design and assemble remotely controlled delivery implants. A nanochannel membrane with gate electrodes and an implantable device containing a drug reservoir, electronics, a battery, and a remote control system will generate a prototype to control, enhance, decrease, interrupt, and reactivate the release of agents. Aim 2) To investigate the tunable and remote controlled release of drugs in vitro. Here, we will demonstrate function of the implant and its broad applicability to biomedical studies involving drugs of different molecular size and physicochemical properties. Aim 3) To test the RF-controlled implant for the tunable delivery of drugs in small and large animals. Devices will be subcutaneously tested in rodents (small implant) and macaques (large implant). Remote modulation of drug delivery will be assessed via pharmacokinetic analysis of a representative drug. Integrity and performances of RF-communications will be simultaneously studied. If successful, the proposed investigation would create a broadly applicable working technology that leverages nanochannel membranes for finely controlled modulation of therapeutic release of a broad spectrum of agents to address biomedical research needs across multiple systems or diseases.

每一种新的药物或治疗方案，无论是基于生物制剂还是化学制剂，都需要 对剂量、制剂、给药方案和 持续时间然而，这些研究是复杂的，昂贵的和耗时的，表明需要一个 多功能和有效的使能工具能够在真实的时间内测试和校正不适当的剂量，持续时间， 和给药频率。在这项研究中，我们将开发一种远程控制的植入式 纳米流体技术，能够精确增加，减少，激活或中断药物 体内递送。该技术具有高度创新性，可提供长期、精细、连续的调制 剂量集中在使用嵌入式门电极和蓝牙低功耗无线电 频率（RF）通信。进一步区分基于三个关键方面：1）静电 纳米通道的门控，2）超低功耗，和3）相对于 药物成分（小分子、蛋白质和纳米颗粒都可以被释放）、动物大小（ 植入物适用于小型和大型动物）和材料组成（廉价组件）。 为了研制这种装置，我们提出了以下实验目标：目标1）设计和组装 远程控制输送植入物一种具有栅极电极和 包含药物储存器、电子器件、电池和远程控制系统的可植入装置 将产生一个原型来控制，增强，减少，中断，并重新激活释放 剂.目的2）研究药物的体外可调远程控制释放。这里我们 将证明植入物的功能及其对生物医学研究的广泛适用性， 不同分子大小和物理化学性质的药物。目的3）测试射频控制的 用于在小型和大型动物中可调节地递送药物的植入物。器械将皮下植入 在啮齿动物（小植入物）和猕猴（大植入物）中进行了测试。药物递送的远程调节 将通过代表性药物的药代动力学分析进行评估。的完整性和业绩 RF通信将同时进行研究。如果成功，拟议的调查将 创造一种广泛适用的工作技术，利用纳米通道膜， 控制调节广谱药剂的治疗释放以解决生物医学 研究需要跨越多个系统或疾病。

项目成果

Long-acting tunable release of amlodipine loaded PEG-PCL micelles for tailored treatment of chronic hypertension.

• DOI: 10.1016/j.nano.2021.102417
• 发表时间: 2021-10
• 期刊: Nanomedicine : nanotechnology, biology, and medicine
• 作者: Di Trani N;Liu HC;Qi R;Viswanath DI;Liu X;Chua CYX;Grattoni A
• 通讯作者: Grattoni A

Intratumoral nanofluidic system enhanced tumor biodistribution of PD-L1 antibody in triple-negative breast cancer.

• DOI: 10.1002/btm2.10594
• 发表时间: 2023-11
• 期刊: Bioengineering & translational medicine
• 影响因子: 7.4

Sustained Intratumoral Administration of Agonist CD40 Antibody Overcomes Immunosuppressive Tumor Microenvironment in Pancreatic Cancer.

• DOI: 10.1002/advs.202206873
• 发表时间: 2023-03
• 期刊: Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Potentiating Antitumor Efficacy Through Radiation and Sustained Intratumoral Delivery of Anti-CD40 and Anti-PDL1.

• DOI: 10.1016/j.ijrobp.2020.07.2326
• 发表时间: 2021-06-01
• 期刊: International journal of radiation oncology, biology, physics
• 作者: Liu HC;Viswanath DI;Pesaresi F;Xu Y;Zhang L;Di Trani N;Paez-Mayorga J;Hernandez N;Wang Y;Erm DR;Ho J;Susnjar A;Liu X;Demaria S;Chen SH;Teh BS;Butler EB;Xuan Chua CY;Grattoni A
• 通讯作者: Grattoni A

Silicon Carbide-Gated Nanofluidic Membrane for Active Control of Electrokinetic Ionic Transport.

• DOI: 10.3390/membranes11070535
• 发表时间: 2021-07-15
• 期刊: Membranes
• 影响因子: 4.2
• 作者: Silvestri A;Di Trani N;Canavese G;Motto Ros P;Iannucci L;Grassini S;Wang Y;Liu X;Demarchi D;Grattoni A
• 通讯作者: Grattoni A