Solvent Evaporator Equipment Supplement to R35GM143101

项目摘要/摘要 生物可降解聚合物在控制体内药物释放方面显示出巨大的效用，改善了 药物疗效，提高药物安全性，并提高患者对药物的依从性。不幸的是，目前 聚合物，如聚(乳酸-乙醇酸)(PLGA)，由于许多原因不是理想的，尽管它们很好地- 报告的生物兼容性。这些材料通常是可大量降解的材料，其行为必须 根据经验确定的，并且对调整累积药物释放曲线的形状的可能性很小 而不是简单地扩展或压缩一级释放动力学。此管理部门的父级奖励 补充提案旨在开发基于表面侵蚀可生物降解的新药物输送系统 能够完全、可预测地控制释放动力学的聚合物，保护封装的生物制品不受 环境应激源，否则会降低其生物活性，并在使用者体内释放多种药物- 定义的顺序。这项工作需要合成光敏表面腐蚀材料，以光为基础 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装载药物 方法。这些步骤中的每一步都需要使用有机溶剂。光引发剂聚合 分布和溶剂介导的药物摄取是在溶剂中进行的，在体外之前必须去除这些溶剂。 或在体内进行评估。到目前为止，溶剂蒸发器是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，避免可能破坏的气泡形成 微粒形态。该工具结合了低压、预定义温度和 离心法，可防止碰撞，只需最少的处理即可快速回收材料 损失。溶剂蒸发器的替代品，我们最近被迫使用了一次我们的15- 使用一年的溶剂蒸发器出现故障，是我们失去的功能的很差的替代品。一次扶轮 对于某些聚合物和有机溶剂，蒸发器可以除去溶剂；然而，这需要更多的 除去溶剂的时间更长(有时用共溶剂进行几次蒸发循环)，需要更多的时间(一次 一天内采样)运行一个样品比使用溶剂蒸发器运行许多样品要少。另外， 在转移和蒸发过程中损失了大量的材料，这一点特别不幸，因为 我们的定制合成、表面腐蚀聚合物的珍贵特性。这项建议寻求财政上的 购买新的溶剂蒸发器-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以前的工具无法操作时失去的功能 同时还通过蒸发高沸点的有机溶剂来增强我们的能力， 例如二甲亚砜(DMSO；沸点，189°C)。我们之前已经确定DMSO是一种很好的 使用溶胀法将药物装载到聚合物中的候选材料，但出于移除方面的考虑而避免了这种方法。

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.