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.

项目摘要/摘要 可生物降解的聚合物表现出了控制体内药物释放的极大效用，改善了 药物效率，提高药物安全性并增加患者对药物的依从性。不幸的是，目前 聚合物，例如聚（乳酸 - 乙醇酸）（PLGA），出于多种原因而不是理想的选择 报告的生物相容性。这些材料通常是散装材料，其行为必须是 经验确定的，不太可能调整累积药物释放曲线的形状 除了简单地扩展或压缩一阶释放动力学。此行政的父母奖 补充建议旨在开发基于表面磨损的可生物降解的新药物输送系统 能够对释放动力学的完全，可预测控制的聚合物保护封装的生物制剂免受 环境压力源否则会降低其生物活性，并在用户中释放多种药物 - 定义的序列。这项工作需要综合光子响应的表面验证材料，基于光的材料 制造以形成聚合物微观结构，在某些情况下是使用聚合物基质肿胀的药物加载 方法。这些步骤中的每一个都必须使用有机溶液。聚合，光引发剂 分布和溶剂介导的药物摄取是在溶液中进行的，必须在体外去除该药物 或体内评估。到目前为止 容器与粘性材料兼容，避免形成可能破坏的气泡 微粒形态。该工具结合了低压的好处，预定义的温度和 离心，阻止撞击，从而使材料快速恢复以最少的处理 损失。溶剂蒸发剂的替代品，我们最近被迫使用15- 一岁的溶剂蒸发器破裂，是我们丢失的功能的替代品。旋转 蒸发器可以 - 对于某些聚合物和有机溶液，可以避免使用溶液。但是，这需要很多 删除解决方案的时间更长（有时与共同溶剂的几个经济周期）需要更多的时间（一个 一天之内的样品）运行一个样品，而不是用溶剂蒸发器运行许多样品。此外， 在转会和经济过程中丢失了大量材料，这尤其不幸，因为 我们定制合成的表面浏览聚合物的宝贵性质。该建议寻求财务 购买新的溶剂蒸发器所需的支持-SP Genevac EZ-2.4 Elite Aupaporator系统。 这件设备将能够恢复我们以前的工具无法操作时丢失的功能 同时还通过具有高沸点的有机解决方案的经济来增强我们的能力，但 例如二甲基磺代（DMSO；沸点，189°C）。我们以前已经确定DMSO是一个好 使用肿胀方法将药物加载到聚合物中的候选者，但由于消除了担忧而避免了它。