Solvent Evaporator Equipment Supplement to R35GM143101

R35GM143101 溶剂蒸发器设备补充

• 批准号: 10799251
• 负责人: Kevin James McHugh
• 金额: $ 5.93万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10799251
• 关键词: 15 year old; Administrative Supplement; Affect; Award; Behavior; Biological Assay; Biological Products; Centrifugation; Custom; Deposition; Devices; Dimethyl Sulfoxide; Drug Delivery Systems; Drug Kinetics; Dryness; Encapsulated; Ensure; Equipment; Excision; Financial Support; Funding; Gel Chromatography; Glass; Glycolates; Grant; Hour; In Vitro; Infiltration; Kinetics; Light; Manufacturer; Mediating; Methacrylates; Methanol; Methods; Molecular Weight; Morphology; National Institute of General Medical Sciences; Nature; Occupations; Organic solvent product; Parents; Pharmaceutical Preparations; Physical condensation; Polymers; Preparation; Procedures; Process; Productivity; Property; Reaction; Recovery; Reporting; Reproducibility; Research; Research Personnel; Running; Sampling; Services; Shapes; Side; Solubility; Solvents; Structure; Surface; Swelling; System; Temperature; Time; Ultraviolet Rays; Vacuum; Vial device; Viscosity; Waste Products; Work; biodegradable polymer; biomaterial compatibility; compliance behavior; cost; crosslink; data quality; drug candidate; drug efficacy; environmental stressor; evaporation; exhaust; experience; experimental study; fabrication; flasks; functional restoration; improved; in vivo; in vivo evaluation; instrument; interest; light intensity; manufacture; medication safety; next generation; novel therapeutics; particle; photocuring; polymerization; pressure; prevent; repaired; seal; success; three dimensional structure; tool; uptake; wasting

PROJECT SUMMARY/ABSTRACT Biodegradable polymers have demonstrated great utility for controlling the release of drugs in vivo, improving drug efficacy, enhancing drug safety, and increasing patient adherence to medication. Unfortunately, current polymers, such as poly(lactic-co-glycolic acid) (PLGA), are not ideal for a number of reasons, despite their well- reported biocompatibility. These materials are generally bulk-degrading materials whose behavior must be empirically determined and offer very little potential for tuning the shape of the cumulative drug release curve other than simply extending or compressing first-order release kinetics. The parent award of this administrative supplement proposal aims to develop new drug delivery systems based on surface-eroding biodegradable polymers that enable full, predictable control over release kinetics, protect encapsulated biologics from environmental stressors that would otherwise diminish their bioactivity, and release multiple drugs in user- defined sequence. This effort requires the synthesis of photo-responsive surface-eroding materials, light-based fabrication to form polymeric microstructures and, in some cases, drug loading using a polymer matrix swelling method. Each of these steps necessitates the use of an organic solvent. Polymerization, photoinitiator distribution, and solvent-mediated drug uptake are performed in solvents, which must be removed prior to in vitro or in vivo evaluation. A solvent evaporator is, by far, the best tool for this job as it works with small reaction vessels, is compatible with viscous materials, and avoids the formation of bubbles that might undermine microparticle morphology. This tool combines the benefits of low pressure, a pre-defined temperature, and centrifugation, which prevents bumping, allowing for the rapid recovery of material with minimal processing losses. The alternatives to a solvent evaporator, which we have recently been forced to employ once our 15- year-old solvent evaporator broke down, are very poor substitutes for the functionality that we lost. A rotary evaporator can—for some polymers and organic solvents—remove the solvent; however, this requires much longer to remove the solvent (sometimes several evaporation cycles with a co-solvent), takes far more time (one sample in one day) to run one sample than it did to run many samples with the solvent evaporator. Additionally, a large quantity of material is lost during transfer and evaporation, which is particularly unfortunate because of the precious nature of our custom-synthesized, surface-eroding polymer. This proposal seeks the financial support necessary to purchase a new solvent evaporator—an SP Genevac EZ-2.4 ELITE evaporator system. This piece of equipment will be able to restore the function that we lost when our previous tool became inoperable while also enhancing our capabilities by enabling the evaporation of organic solvents with high boiling points, such as dimethyl sulfoxide (DMSO; boiling point, 189 °C). We have previously identified DMSO to be a good candidate for drug loading into polymers using the swelling method, but have avoided it due to removal concerns.

项目概要/摘要 生物可降解聚合物已被证明在控制体内药物释放、改善 药物疗效，提高药物安全性，提高患者服药依从性。不幸的是，目前 聚合物，例如聚（乳酸-乙醇酸）（PLGA），由于多种原因并不理想，尽管它们具有良好的 报道了生物相容性。这些材料通常是整体降解材料，其行为必须是 凭经验确定，调整累积药物释放曲线形状的可能性很小 而不是简单地扩展或压缩一级释放动力学。本次行政家长奖 补充提案旨在开发基于表面侵蚀可生物降解的新型药物输送系统 聚合物能够全面、可预测地控制释放动力学，保护封装的生物制剂免受 环境压力会降低其生物活性，并在使用者体内释放多种药物 定义的序列。这项工作需要合成光响应表面侵蚀材料、光基材料 制造以形成聚合物微结构，并且在某些情况下，使用聚合物基质溶胀来负载药物 方法。这些步骤中的每一个都需要使用有机溶剂。聚合、光引发剂 分布和溶剂介导的药物摄取是在溶剂中进行的，在体外之前必须将其除去 或体内评价。到目前为止，溶剂蒸发器是完成这项工作的最佳工具，因为它的反应很小 容器，与粘性材料兼容，并避免形成可能破坏的气泡 微粒形态。该工具结合了低压、预定义温度和 离心，可防止碰撞，从而以最少的处理快速回收材料 损失。溶剂蒸发器的替代品，我们最近被迫在我们的 15- 使用了一年的溶剂蒸发器坏了，对于我们失去的功能来说是非常差的替代品。旋转式 对于某些聚合物和有机溶剂，蒸发器可以去除溶剂；然而，这需要很多 去除溶剂的时间更长（有时使用共溶剂进行几次蒸发循环），需要更多的时间（一次 一天内运行一个样品）比使用溶剂蒸发器运行多个样品要好。此外， 在转移和蒸发过程中会损失大量材料，这是特别不幸的，因为 我们定制合成的表面侵蚀聚合物的珍贵本质。该提案寻求财政 购买新溶剂蒸发器（SP Genevac EZ-2.4 ELITE 蒸发器系统）所需的支持。 这台设备将能够恢复我们之前的工具无法使用时失去的功能 同时还通过蒸发高沸点有机溶剂来增强我们的能力， 例如二甲基亚砜（DMSO；沸点189℃）。我们之前已经确定 DMSO 是一种很好的 使用溶胀方法将药物装载到聚合物中的候选药物，但由于去除问题而避免使用。