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Investigation of Cell Media and Aminoglycoside Hydrogel Properties for Cancer Cell Dormancy

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In a dormant state, cancer cells survive chemotherapy leaving the opportunity for cancer cell relapse and metastasis ultimately leading to patient death. A novel aminoglycoside-based hydrogel ‘Amikagel’ developed in Dr. Rege’s lab serves as a platform for a 3D tumor

In a dormant state, cancer cells survive chemotherapy leaving the opportunity for cancer cell relapse and metastasis ultimately leading to patient death. A novel aminoglycoside-based hydrogel ‘Amikagel’ developed in Dr. Rege’s lab serves as a platform for a 3D tumor microenvironment (3DTM) mimicking cancer cell dormancy and relapse. Six Amikagels of varying mechanical stiffness and adhesivities were synthesized and evaluated as platforms for 3DTM formation through cell viability and cell cycle arrest analyses. The impact of fetal bovine serum concentration and bovine serum albumin concentration in the media were studied for their impact on 3DTM formation. These experiments allow us to identify the best possible Amikagel formulation for 3DTM.

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2016-05

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Synthesis of Dual Layered Microparticles for Tunable Delayed Release Profile

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The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which

The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA shell surrounding the PLGA core. The microparticles were loaded with bovine serum albumin (BSA) and different volumes of ethanol were added to the PLA shell phase to alter the porosity and release characteristics of the BSA. Different amounts of ethanol varied the total loading percentage of the BSA, the release profile, surface morphology, size distribution, and the localization of the protein within the particles. Scanning electron microscopy images detailed the surface morphology of the different particles. Loading the particles with fluorescently tagged insulin and imaging the particles through confocal microscopy supported the localization of the protein inside the particle. The study suggest that ethanol alters the release characteristics of the loaded BSA encapsulated in the microparticles supporting the use of a polar, protic solvent as a tool for tuning the delayed release profile of biological proteins.

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2015-05

Statistical Modeling of Drug Release from Spherical Surface-Degrading Particle Batch

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The goal of this research project is to create a Mathcad template file capable of statistically modelling the effects of mean and standard deviation on a microparticle batch characterized by the log normal distribution model. Such a file can be

The goal of this research project is to create a Mathcad template file capable of statistically modelling the effects of mean and standard deviation on a microparticle batch characterized by the log normal distribution model. Such a file can be applied during manufacturing to explore tolerances and increase cost and time effectiveness. Theoretical data for the time to 60% drug release and the slope and intercept of the log-log plot were collected and subjected to statistical analysis in JMP. Since the scope of this project focuses on microparticle surface degradation drug release with no drug diffusion, the characteristic variables relating to the slope (n = diffusional release exponent) and the intercept (k = kinetic constant) do not directly apply to the distribution model within the scope of the research. However, these variables are useful for analysis when the Mathcad template is applied to other types of drug release models.

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2021-05

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Light-Activated Sealants for Internal Organ Repair and Healing

Description

The current clinical gold standards for tissue sealing include sutures, staples, and glues, however several adverse effects limit their use. Sutures and staples inherently cause additional trauma to tissue surrounding the wound, and glues can be lacking in adhesion and

The current clinical gold standards for tissue sealing include sutures, staples, and glues, however several adverse effects limit their use. Sutures and staples inherently cause additional trauma to tissue surrounding the wound, and glues can be lacking in adhesion and are potentially inflammatory. All three also introduce risk of infection. Light-activated tissue sealing, particularly the use of near-infrared light, is an attractive alternative, as it localizes heat, thereby preventing thermal damage to the surrounding healthy tissue. Previous work identified a glutaraldehyde-crosslinked chitosan film as a lead sealant for gastrointestinal incision sealing, but in vivo testing resulted in tissue degradation in and around the wound. The suggested causes for this degradation were excess acetic acid, endotoxins in the chitosan, and thermal damage. A basic buffer wash protocol was developed to remove excess acid from the films following fabrication. UV-Vis spectroscopy demonstrated that following the wash, films had the same concentration of Indocyanine green as unwashed films, allowing them to absorb light at the same wavelength, therefore showing the wash did not affect the film’s function. However subsequent washes led to degradation of film mass of nearly 20%. Standard chitosan films had significantly greater mass gain (p = 0.028) and significantly less subsequent loss (p= 0.012) than endotoxin free chitosan-films after soaking in phosphate buffered saline for varying durations , while soaking duration had no effect (p = 0.332). Leak pressure testing of films prepared with varying numbers of buffer washes, laser temperature, and lasering time revealed no significant interaction between any of the 3 variables. As such, it was confirmed that proceeding with in vivo testing with the buffer wash, various lasering temperatures, and laser times would not affect the sealing performance of the films. Future investigation will involve characterization of additional materials that may be effective for sealing of internal wounds, as well as drug loading of agents that may hasten the healing process.

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2022-05