Polymer Nanoparticle Characterization and Applications for Drug Delivery

dc.contributor.authorRoberts, Rose A.en
dc.contributor.committeechairFoster, Earl Johanen
dc.contributor.committeememberWhittington, Abby Rebeccaen
dc.contributor.committeememberGourdie, Robert G.en
dc.contributor.committeememberEdgar, Kevin Jen
dc.contributor.departmentMaterials Science and Engineeringen
dc.date.accessioned2021-07-24T06:00:06Zen
dc.date.available2021-07-24T06:00:06Zen
dc.date.issued2019-01-30en
dc.description.abstractNanoparticle usage continues to increase in everyday products, from cosmetics to food preservation coatings, drug delivery to polymer fillers. Their characterization and synthesis is of utmost importance to ensure safety and improved product quality. Nanoparticles can be sourced naturally or synthetically fabricated. Cellulose nanocrystals (CNCs) are rod-like nanoparticles that can be isolated from nature. Reliable methods of characterization are necessary to ensure quality control. However, their physical characteristics cause challenges for imaging under transmission electron microscopy (TEM) with a high enough resolution for dimensional analysis. Heavy metal staining such as radioactive uranyl acetate is often used to increase contrast and TEM sample substrate preparation techniques often use expensive equipment such as glow discharge in order to prevent CNC agglomeration. A method to reliably produce TEM images of CNCs without using radioactive stains or expensive glow discharge equipment was developed, using a vanadium-based stain branded NanoVan® and bovine serum albumin to keep CNCs dispersed while drying on the TEM substrate. Due to their aspect ratio, there is also concern of toxicity to the lungs. The concentration of CNCs in air in production facilities must be monitored, but there is currently no method tailored to CNCs. A method using UV-vis spectroscopy, dynamic light scattering, TEM, and scanning mobility particle sizer in conjunction with impinger collectors was developed for monitoring aerosolized CNC concentration. Synthetic nanoparticles are often used for controlled drug delivery systems. A new peptide drug termed αCT1 has been shown to interact with cell communication in a way that promotes wound healing, reduces inflammation and scarring, and aids in cancer therapy. However, the peptide's half-life in the body is estimated to be less than a day, which is not conducive to long-term treatments. Controlling its release into the body over several weeks can decrease the number of doses required, which is especially useful for glioblastoma treatment. Poly(lactic-co-glycolic acid) (PLGA) is often used for drug encapsulation since it hydrolyzes in the body and is biocompatible. Two methods of αCT1 encapsulation in PLGA were explored. It was found that flash nanoprecipitation increased loading of αCT1 in the particles by 1-2 orders of magnitude compared with the double emulsion method. Particles released αCT1 over three weeks and were non-cytotoxic.en
dc.description.abstractgeneralNanoparticle usage continues to increase in everyday products, from cosmetics to food preservation coatings, drug delivery to polymer fillers. Understanding the nature of nanoparticles is important to ensure safety and quality of commercial products, and production of particles allows for tailoring for specific applications. In this work, a technique to more easily create samples of cellulose nanocrystals (CNCs) for electron microscopy is developed. Electron microscopy can then be used to measure the size of these rod-like particles. Then, the technique is used to help develop a method to measure the concentration of CNCs in air. CNCs may irritate the lungs, so development of a way to measure their concentration in air is important to ensure safety of plant workers and consumers of CNCs. Characterization techniques of CNCs were used for synthesized particles used for brain cancer treatment. Synthesized particles contain the drug αCT1, which has been shown to reduce glioblastoma, or brain cancer, from becoming resistant to chemotherapy. These particles were made using poly(lactic-co-glycolic acid) (PLGA), a polymer that degrades in the body into lactic acid and glycolic acid. PLGA particles released αCT1 over three weeks and are of a size that is compatible with the brain. However, loading of the drug was low when using the first synthesis method. By switching particle synthesis methods, drug loading in the particles was increased by 1-2 orders of magnitude.en
dc.description.degreePHDen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:18507en
dc.identifier.urihttp://hdl.handle.net/10919/104384en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectpoly(lactic-co-glycolic acid)en
dc.subjectcellulose nanocrystalsen
dc.subjectdrug deliveryen
dc.titlePolymer Nanoparticle Characterization and Applications for Drug Deliveryen
dc.typeDissertationen
thesis.degree.disciplineMaterials Science and Engineeringen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePHDen

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