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To learn more about Dr Sung Joon Kim's lab, please visit:
Me operating the Horiba SZ-100V2, the Dynamic Light Scattering (DLS) instrument, for characterizing solid lipid nanoparticles (SLNs).
Synthesis and Characterization of Solid Lipid Nanoparticles (SLNs) (in progress)
Lipid nanoparticles (LNPs) and solid lipid nanoparticles (SLNs) are at an exciting juncture in the history of biomedical research. They are drug delivery vehicles made of lipid (or fat) molecules, which encapsulate the drug. LNPs have already impacted millions' lives for the better through the COVID-19 vaccines made by Pfizer/BioNTech, Moderna and others, which have mRNA encapsulated inside the particles. Even before that, the first LNP-based drug to be approved by the FDA in 2018, Patisiran, has been used to treat polyneuropathies for patients with hereditary transthyretin amyloidosis (hATTR).
My Honors Senior Thesis focuses on the optimization of fatty acyl chain length for making small and stable SLNs.
LNPs and SLNs differ from other drug delivery mechanisms in that they can travel across the gut better, they can travel through the lymphatic system, and even across the blood-brain barrier, to deliver their payload - places which only lipophilic (fat-soluble) molecules tend to pass through. This has been useful for delivering molecules like mRNA, which are unstable and are degraded easily by the body's nuclease enzymes, and antibiotics, which usually have a hard time traveling through the mucus of patients with tuberculosis and similar respiratory conditions. At the Kim Lab, we are working to synthesize solid lipid nanoparticles that are both small (i.e., whose diameter is in the range of hundreds of nanometers) and exhibit long-term stability, even without refrigeration. We anticipate this will be instrumental in delivering therapies to communities in the world where fridges for storing drugs are hard to come by. Once they are synthesized, the particle formulation is analyzed using dynamic light scattering (DLS), also known as photon correlation spectroscopy (PCS), to determine their size distribution and zeta potential. The zeta potential is a measure of the particles' surface charge, and it is good for particles to have the same kind of charge on their surface, so that they repel each other and don't aggregate (or clump together). My colleagues and I take turns to carry out the synthesis, and we collaborate during the data analysis stage as well. I have written a Python script that parses the instrument files and loads the data into Excel.
The next stage of the project, which I will be focusing on, is to prepare nanoparticles loaded with antibiotics for the treatment of tuberculosis and other respiratory diseases caused by pathogens, and conduct bioassays to compare the efficacy of drug delivery to lung tissue using SLN compared to unencapsulated drug. For this project, I have been selected as a Dow Scholars Undergraduate Research (SURE) scholar for the 2023-2024 academic year, and I will be receiving mentorship from Dow as well as a stipend to assist with my research. This research will also contribute to my Senior Honors Thesis, which I will submit in April 2024.
Data Visualization of Effect of Daptomycin on Peptidoglycan Biosynthesis in Enterococcus faecalis bacteria (article published in Scientific Reports)
This was one of the first projects assigned to me after joining the Kim Lab in my sophomore year: producing a visualization (or diagram) for mass spectrometry fragment data of the peptidoglycan (cell wall material) of the Gram-positive bacterium Enterococcus faecalis (or E. faecalis) treated with the antibiotic daptomycin.
E. faecalis is of interest because, while it lives harmlessly inside our gut, it can cause deadly infections when it spreads to the blood or other areas, especially for at-risk patients in hospitals (immunocompromised individuals or organ transplant recipients). It is now a common multi-drug-resistant bacteria. A defining feature of Gram-positive bacteria, such as E. faecalis, is that outside their primary cell membrane, they have a thick protective layer of peptidoglycan (PG), a two-dimensional polymer made of sugars and amino acids. All other known bacteria, which are Gram-negative, have only a thin layer of peptidoglycan, and a second cell membrane covering it. Daptomycin, a lipopeptide antibiotic (see top figure), is effective against multi-drug-resistant Gram-positive bacteria such as staphylococci, streptococci and enterococci (which, of course, E. faecalis belongs to). It has long been hypothesized that daptomycin kills these groups of bacteria by perforating the peptidoglycan layer. An additional mechanism of action, as this paper by Dr Kim's group aims to show, is that the drug inhibits the biosynthesis of peptidoglycan (i.e., it gets in the way of the bacteria making new peptidoglycan in the first place).
The visualization I made as part of the paper (see bottom figure), shows the changes in the patterns of crosslinking (number of crosslinks between individual PG strands), alanylation (number of L-alanine groups in the peptide bridge added or removed) and acetylation (number of acetyl groups in the sugar portion added or removed), in a daptomycin-sensitive strain of E. faecalis, both untreated populations and populations treated with the drug.
This work has been published in an article in Scientific Reports in July 2023:
Rimal, B., Chang, J., Liu, C., Rashid, R., Singh, M., & Kim, S. J. (2023). The effects of daptomycin on cell wall biosynthesis in Enterococcal faecalis. Scientific Reports, 13(1), 12227. https://doi.org/10.1038/s41598-023-39486-8
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