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.

项目总结/摘要 可生物降解的聚合物已被证明在控制药物在体内的释放、改善生物相容性和生物相容性方面具有很大的实用性。 药物功效、增强药物安全性和增加患者对药物的依从性。不幸的是，目前 聚合物，如聚（乳酸-共-乙醇酸）（PLGA），由于多种原因不是理想的，尽管它们具有良好的- 报道了生物相容性。这些材料通常是本体降解材料，其行为必须是可降解的。 并且提供很少的调整累积药物释放曲线形状的可能性 而不是简单地延长或压缩一级释放动力学。本行政裁决的父裁决 一项补充提案旨在开发基于表面侵蚀可生物降解的新药物递送系统 能够完全、可预测地控制释放动力学的聚合物， 环境应激源，否则会降低其生物活性，并在用户中释放多种药物， 定义序列。这项工作需要合成光响应表面侵蚀材料，光基 制造以形成聚合物微结构，以及在某些情况下，使用聚合物基质溶胀的药物负载 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 药物分布和溶剂介导的药物摄取在溶剂中进行，这些溶剂必须在体外释放之前除去。 或体内评价。溶剂蒸发器是迄今为止最好的工具，因为它的工作与小反应 容器，与粘性材料相容，并避免形成气泡， 微粒形态该工具结合了低压、预定义温度和 离心分离，防止碰撞，允许以最少的处理快速回收材料 损失溶剂蒸发器的替代品，我们最近被迫使用，一旦我们的15- 一年前的溶剂蒸发器坏了，是我们失去的功能的非常差的替代品。旋转 对于某些聚合物和有机溶剂，蒸发器可以除去溶剂;然而，这需要很大的 除去溶剂的时间更长（有时用共溶剂进行几个蒸发循环），需要更多的时间（一个 一天中的样品）来运行一个样品比用溶剂蒸发器来运行许多样品所做的要少。此外，本发明还 在转移和蒸发过程中损失了大量的材料，这是特别不幸的，因为 我们定制合成的表面腐蚀聚合物的珍贵特性。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。 这件设备将能够恢复功能，我们失去了当我们以前的工具变得无法操作 同时还通过使具有高沸点的有机溶剂蒸发来增强我们的能力， 例如二甲基亚砜（DMSO;沸点，189 °C）。我们以前已经确定DMSO是一种良好的 使用溶胀方法将药物负载到聚合物中的候选物，但由于去除问题而避免了它。