Development of Blister packs for intradermal delivery of high-viscosity suspensions

开发用于皮内输送高粘度悬浮液的泡罩包装

• 批准号: 10553209
• 负责人: Jeremy Marston
• 金额: $ 18.37万
• 依托单位: TEXAS TECH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10553209
• 关键词: Address; Back; Biological; Bulla; Cavia; Communicable Diseases; DNA; DNA Vaccines; Dermal; Developing Countries; Development; Devices; Dose; Dyes; Ebola; Environment; Family suidae; Gene Expression; Goals; Grant; HIV; Head; Hepatitis B; Human; Image; Immune System Diseases; Immune response; Injectable; Injections; Jet Injections; Liquid substance; Marketing; Mass Immunization; Methods; Middle East Respiratory Syndrome; Modeling; Needles; Needlestick Injuries; Nucleic Acids; Patients; Pharmaceutical Preparations; Phobias; Polymers; Public Health; Research; Self Administration; Skin; Skin Tissue; Statistical Factor Analysis; Suspensions; Techniques; Technology; Testing; Tissues; Training; United States National Institutes of Health; Vaccination; Viscosity; ZIKA; clinically relevant; compliance behavior; cost; design; fabrication; hypodermic needle; improved; in vivo; intradermal injection; microCT; monomer; new technology; novel strategies; nucleic acid delivery; pain reduction; plasmid DNA; pressure; prototype; technology platform; wasting

Project summary Injectable drugs constitute a $400+ billion market worldwide, and the range of devices for delivery is expanding to improve factors such as patient compliance, reduced pain, self-administration, and delivery efficiency. Intradermal delivery is especially pertinent in this regard for potential confluences of reduced pain, fast immune response and fractional dose vaccination. Also high on the priority list for delivery technologies are nucleic acids, which are seen as promising biological drugs for a range of immune disorders and infectious diseases. There are currently over 900 biological drugs on the market or in development. Amongst these, plasmid DNA vaccines have been widely studied over the last two decades and are being developed for Ebola, MERS, Zika, Hepatitis B, and HIV. However, a major obstacle is the method of delivery due to the large physical size of the molecules, which can render products that are high-viscosity, creating issues for injectability with standard hypodermic needles. This exploratory grant will develop prototype devices, based on blister-pack concepts, for intradermal injection of viscous suspensions, with the primary target being DNA products. Guided by approaches using hollow microneedles, we will fabricate and test single-orifice and multi-orifice modules that target intradermal delivery. The prototypes will be tested across a broad range of fluid viscosities and existing drugs. The proposed study comprises a proof-of-concept for our devices using ex-vivo tissues, and limited in-vivo studies using guinea pigs, a clinically relevant model for intradermal delivery. The overarching goal is to optimize intradermal delivery, specifically with regards to high-viscosity products in order to advance the feasibility of widespread DNA vaccination.

项目总结 可注射药物构成了全球4000多亿美元的市场，以及用于给药的设备范围 正在扩大以改善患者依从性、减轻疼痛、自我管理、 和交付效率。皮内给药在这方面尤其适用于潜在的 减轻疼痛、快速免疫反应和分次接种疫苗的合流。也是很高的 优先考虑的交付技术是核酸，它们被视为很有前途的生物 治疗一系列免疫紊乱和传染病的药物。目前有900多家 市场上或正在开发的生物药物。其中，质粒DNA疫苗有 在过去20年里被广泛研究，目前正在为埃博拉、中东呼吸综合征、寨卡病毒 乙肝和艾滋病毒。然而，由于大量的实物，一个主要的障碍是交付方法 分子的大小，这可能会产生高粘度的产品，这会给 标准皮下注射针头的可注射性。 这笔探索性赠款将根据泡罩包装的概念开发原型设备，用于 皮内注射粘性悬浮液，主要目标是DNA产品。引导式 通过使用中空微针的方法，我们将制造和测试单孔和多孔 以皮内给药为目标的模块。原型将在广泛的 液体粘度和现有药物。拟议的研究包括为我们的 使用体外组织的设备，以及有限的使用豚鼠的体内研究，临床相关 皮内给药的模型。首要目标是优化皮内给药， 特别是关于高粘度产品，以推进 广泛的DNA疫苗接种。