Solvent Evaporator Equipment Supplement to R35GM143101

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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.