Physical Stability of Liposomes

Liposomes have proven to be effective nanocarriers of various drugs and pharmaceutical compounds. Their spherical lipid bilayer composition enables the entrapment of such molecules in their internal aqueous environment. A concern with these nanocarriers is their stability over time. Specifically, I investigated how liposomes degrade in different pH buffer solutions over an 8-day period. Fabrication of liposomes was accomplished by extruding DOPC lipids in buffer solutions of varying pH’s through a 100 nm pore size polycarbonate membrane. The samples were stored in a 70 °C recirculatory bath throughout the experiment and were tested daily. To characterize degradation, I utilized Dynamic Light Scattering (DLS) and UV-Vis spectroscopy. The DLS was used to determine average liposome size and the UV-Vis was used to determine light transmittance. We found liposome diameter increased for all pH’s with a significant increase in polydispersity among all samples. While some pH’s did cause greater increases than others, we were unable to make a strong correlation between the rate of degradation and the pH. The UV-Vis was not useful as the initial solutions were too opaque. The overall increase in polydispersity is significant because it points towards a “soup” of particles that may form from the various degradation products. These products may include various sized liposomes, long cylindrical micelles, and surfactant particles. Further study of these particles may give insight into the degradation processes occurring.

Stroke Rehab Using Negative Stiffness Compliant Shell Mechanisms

The goal of this project was to characterize, verify, and optimize compliant shell geometry that exhibited prolonged negative stiffness. Because research into devices exhibiting negative stiffness is limited, this project added to basic scientific knowledge about such mechanical structures and added to the field’s understanding of them. In addition to this, this research worked towards helping patients in stroke rehabilitation in their journeys of recovery. The approach to this project was greatly motivated by the need for negative stiffness within a rehabilitation device. This is precisely what maximizes the efficiency of repetitive rehabilitation exercises, such as bending of the fingers for hand recovery after a stroke, which was my focus.

Diffusion in Macroscopically Layered Polymer Gels

Transdermal drug delivery is a vital mechanism for skincare, hormone replacement, and other biomedical applications. Organic polymer gels have been recently identified as candidates for this drug delivery mechanism. Our present work focuses on controlling model drug release rate in a layered polymer gel system consisting of multiple organogels and a polystyrene backing. Typically, one organogel contains a diffusion probe [AOT (sodium bis(2-ethylhexyl)sulfosuccinate)], tri-block copolymer, and an organic solvent whereas the other contains only tri-block copolymer and organic solvent. The tri-block copolymer forms a physically crosslinked network within the gels that consists of spherical polystyrene domains and a plasticized rubbery matrix consisting of ethylene-co-butylene and aliphatic mineral oil (organic solvent). The matrix phase is fluid-like and amenable to mass transport, which allows for probe diffusion. Using Fourier Transform Infrared (FTIR) spectroscopy, the overall probe release rate, which stems from this diffusion, can be tracked. In particular, we are interested in the comparison between the aforementioned layered systems and a ‘traditional’ system with a single organogel containing the AOT diffusion probe. We also seek to investigate how changing the tri-block copolymer concentration of the barrier organogel layer – that which contains no AOT – changes the overall diffusion probe release rate. Our measurements show that the release rate of layered systems exhibits a time-delay phenomenon. Furthermore, systems with higher tri-block copolymer concentration in the barrier layer exhibit a longer time delay.

Impact of Morphology and Polymorph on Behavior of Succinic Acid Aerosols in Mixtures with Ammonium Sulfate

Particles on the scale of nanometers are incredibly important in atmospheric chemistry due to their complex role as aerosols in the atmosphere. Atmospheric aerosols and their morphologies directly impact cloud formation, which in turn affects global warming and climate change modeling. In this project, a system of succinic acid, a dicarboxylic acid, and ammonium sulfate, an inorganic salt, was studied as both are commonly found in atmospheric aerosols. Aerosol systems are commonly studied by analyzing their size distributions, and it is expected that most systems produce a Gaussian (normal) size distribution. However, the succinic acid/ammonium sulfate system is noteworthy for containing aerosols with a bimodal size distribution. One plausible explanation for the observed bimodal size distribution is related to the polymorphism of succinic acid, as different crystal structures could produce different particle sizes.
This project utilized a syringe pump to feed aqueous solutions of varying concentrations and mixing ratios of succinic acid and ammonium sulfate into an atomizer to produce nanoscale particles. These particles were then dried and analyzed in a Scanning Mobility Particle Sizer (SMPS) system to obtain size distribution data. To test for the presence of different polymorphs in solutions of succinic acid and ammonium sulfate, particles were collected using a cascade impactor to then be analyzed with powder x-ray diffraction (PXRD) and scanning electron microscopy (SEM). The collected data allowed for the characterization of the succinic acid/ammonium sulfate system at different concentrations and mixtures of solution.

How Many Passes Does it Take?
An Investigation to Determine the Optimal Number of Liposome Extrusion Cycles

Liposomes are lipid-based nanoparticles commonly known for their drug carrying capacity and value in membrane and nanoreactor research. One commonly used method of fabricating liposomes of particular size is membrane extrusion where liposomes are pushed through a porous membrane and form smaller liposomes. However, the details pertaining to liposome extrusion, such as the number of passes, membrane pore sizes, and pre-extrusion sample preparation, vary between labs. The goal of this project is to establish a relationship between the number of passes through a track-etched, polycarbonate membrane, and the average diameter and lamellarity of extruded liposomes. To investigate, we extrude samples to different amounts varying from 1 to 1,000 passes and measure the average hydrodynamic diameter and diameter distribution of each using dynamic light scattering (DLS). We measure lamellarity with small angle x-ray scattering (SAXS) and cryogenic transmission electron microscopy (CryoTEM). When liposome size distribution and lamellarity data start to flatten out, it is suggested that extrusion has been completed, and further extruding would not change the liposome size and lamellarity. These results provide researchers with the optimal number of passes for liposome extrusion that will allow them to form ideal distributions in the shortest amount of time.