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.

每一种新药或治疗方案，无论是基于生物制剂还是化学制剂，都需要 为评估剂量、配方、给药方案和给药方案而进行的广泛调查 期间。然而，这些研究复杂、昂贵且耗时，表明需要 多功能且有效的工具可以实时测试和纠正不适当的剂量、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 以使用嵌入式栅电极和蓝牙低功耗无线电为中心的剂量 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，以及 3) 植入的多功能性 药物成分（小分子、蛋白质和纳米颗粒都可以释放）、动物大小（ 植入物适用于小型和大型动物）和材料成分（便宜的组件）。 为了开发该装置，我们提出以下实验目标： 目标 1) 设计和组装 远程控制输送植入物。具有栅电极和 包含药物储存器、电子设备、电池和远程控制系统的植入式设备 会生成一个原型来控制、增强、减少、中断、重新激活释放 代理。目标2）研究体外药物的可调和远程控制释放。在这里，我们 将展示植入物的功能及其在涉及生物医学研究的广泛适用性 不同分子大小和理化性质的药物。目标 3) 测试 RF 控制 用于在小型和大型动物体内可调药物输送的植入物。装置将植入皮下 在啮齿动物（小植入物）和猕猴（大植入物）中进行了测试。药物输送的远程调节 将通过代表性药物的药代动力学分析进行评估。的诚信和表现 射频通信将同时进行研究。如果成功，拟议的调查将 创建一种广泛适用的工作技术，利用纳米通道膜精细 控制调节广谱药物的治疗释放以解决生物医学问题 跨多个系统或疾病的研究需求。

项目成果

Long-acting refillable nanofluidic implant confers protection against SHIV infection in nonhuman primates.

长效可再填充纳米流体植入物可以保护非人类灵长类动物免受 SHIV 感染。

• 发表时间: 2023-06-28
• 影响因子: 17.1
• 作者: Pons;Di Trani, Nicola;Capuani, Simone;Campa;Nehete, Bharti;Sharma, Suman;Shelton, Kathryn A;Bushman, Lane R;Abdelmawla, Farah;Williams, Martin;Roon, Laura;Nerguizian, David;Chua, Corrine Ying Xuan;I
• 通讯作者: I

Advanced implantable drug delivery technologies: transforming the clinical landscape of therapeutics for chronic diseases.

先进的植入式药物输送技术：改变慢性病治疗的临床格局。

• 发表时间: 2019-05-18
• 影响因子: 2.8
• 作者: Pons;Ballerini, Andrea;Sakamoto, Jason;Grattoni, Alessandro
• 通讯作者: Grattoni, Alessandro

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

通过放射和持续瘤内递送抗 CD40 和抗 PDL1 增强抗肿瘤功效。

• 发表时间: 2021
• 作者: Liu, Hsuan;Viswanath, Dixita I;Pesaresi, Federica;Xu, Yitian;Zhang, Licheng;Di Trani, Nicola;Paez;Hernandez, Nathanael;Wang, Yu;Erm, Donald R;Ho, Jeremy;Susnjar, Antonia;Liu, Xuewu;Demaria, Sandra;Chen, Shu;Teh, Bin
• 通讯作者: Teh, Bin

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

用于主动控制动电离子传输的碳化硅门控纳流膜。

• 发表时间: 2021-07-15
• 影响因子: 4.2
• 作者: Silvestri, Antonia;Di Trani, Nicola;Canavese, Giancarlo;Motto Ros, Paolo;Iannucci, Leonardo;Grassini, Sabrina;Wang, Yu;Liu, Xuewu;Demarchi, Danilo;Grattoni, Alessandro
• 通讯作者: Grattoni, Alessandro

Microfluidic device for the analysis of MDR cancerous cell-derived exosomes' response to nanotherapy.

用于分析 MDR 癌细胞来源的外泌体对纳米疗法的反应的微流体装置。

• 发表时间: 2019-03-25
• 影响因子: 2.8
• 作者: Qi, Ruogu;Zhu, Guixian;Wang, Yu;Wu, Suhong;Li, Shengliang;Zhang, Dechen;Bu, Yang;Bhave, Gauri;Han, Ruixuan;Liu, Xuewu
• 通讯作者: Liu, Xuewu