Nanoparticle delivery to specific locations within the brain requires the ability to control transport properties of the nanoparticle platform. Neurological injury or disease is not generally limited to one location or one cell type. A therapeutic or diagnostic platform must have the ability to move from the point of access in the brain to diffuse disease-related cells. Nanoparticles with no electrostatic, hydrophobic, or hydrogen bonding interactions within the brain microenvironment are classified as brain-penetrating. These brain-penetrating nanoparticles (BPN) can determine the steric limitations of nanoparticle transport within the brain microenvironment, and can characterize microrheological properties of the brain extracellular space. Therefore, adequate characterization of nanoparticle physicochemical properties in physiologically relevant solutions is critical to understanding nanoparticle behavior within the brain microenvironment. Here, we developed a methodology to assay nanoparticle size, surface charge, and polydispersity in the presence of cerebrospinal fluid (CSF), the primary medium that nanoparticles are exposed to in the brain. Typically nanoparticles are characterized in low concentration salt solutions (i.e 10mM NaCl) or in serum, which does not contain any unbound divalent ions, unlike CSF. We demonstrated that the hydrodynamic diameter measured in CSF is 10-20 nm larger than that measured in NaCl or serum, and that surface charge is more negative in CSF. In addition, we saw a decrease in nanoparticle stability in CSF compared to NaCl or serum. This methodology for characterization of nanoparticles in CSF, with comparison to literature standards, will be useful in determining critical nanoparticle physicochemical properties for brain penetration in the presence of brain microenvironment mediums like CSF.

Sore throat is one of the top reasons that adults and children visit their primary physician. Group A streptococcus bacteria is a significant contributor to the prevalence of sore throat and is linked to roughly 11,300 invasive disease cases per year, with 1,800 of those leading to death in the United States alone. Lateral flow assays are a currently available rapid diagnostic of group A strep, but suffer from poor clinical sensitivity, thus requiring additional time consuming and expensive throat cultures for confirmation of negative rapid test results. The clinical sensitivity of commercial rapid immunoassays is limited by its relatively high limit of detection (LoD). The incorporation of electrokinetic techniques, such as isotachophoresis (ITP), has been shown to improve the limit of detection in surface reaction biosensors. ITP concentrates small amounts of colloidal gold-labeled target protein into a band at the interface between a fast-moving leading electrolyte (LE) and a slower trailing electrolyte (TE), which travels across a porous nitrocellulose membrane to a capture protein test line. The reaction between target and capture protein is greatly accelerated due to the high concentration of target protein in the ITP band, consequently improving test sensitivity compared to standard LF tests. Our previous work demonstrated the ability of ITP to lower the limit of detection of fluorescent proteins in comparison to a lateral flow assay. We hypothesized that previous performance enhancement from ITP in a one-site colorimetric assay could be attained in an infectious disease sandwich assay. In this work, we show that integration of ITP into a strep sandwich immunoassay, by incorporating protein extraction chemistry into the LE solution, exhibits two orders-of-magnitude LoD compared to commercial rapid lateral flow assays. We also achieved 75x improvement in analytical sensitivity.

Engineering metabolic pathways in bacteria requires regulation of cellular biology with predictable genetic control devices. Characterizing these controls is key to optimizing biochemical pathways for the sustainable production of high value chemicals. In prokaryotes, small RNA (sRNA) downregulate gene expression by antisense binding to messenger RNA (mRNA) transcripts. The relative ease of re-engineering sRNA targets by replacing its antisense targeting sequence makes sRNA an ideal candidate for implementing post-transcriptional controls in metabolic engineering. In previous work, we incorporated sRNA into metabolite-responsive RNA controllers, but in many cases did not observe the hypothesized trends in mRNA repression. However, we observed the lack of secondary structure within the antisense targeting sequence correlated with higher mRNA repression. To understand these effects and refine the functionality of our constructs, we built a range of new sRNA devices with additional sequence at the 5’ end. We targeted the sRNA to repress fluorescent protein expression, and used functional assays to measure fluorescence across a range of sRNA induction levels. We hypothesized that sRNA carrying a 5’ hairpin will result in greater repression than sRNA lacking structure at the 5’ end, and that base-pairing interactions between the 5’ sequence and the targeting sequence will lead to lower repression. This work aids in the development of rational design principles for using sRNA in RNA-based controls. By understanding the effects of sRNA structure, we will be better able to expand the post-transcriptional controls available to metabolic engineers. Ultimately, this extends our understanding of cellular biochemistry, while providing novel means by which to optimize engineered biochemical pathways.

Continued advances in energy technologies have allowed for the increased utilization of renewable energy sources. However, energy storage is needed to provide power during peak hours. Flow batteries offer a convenient solution to the problem of storing large amounts of energy while remaining relatively cost efficient. One of the most expensive parts of a flow battery is the proton conducting membrane that separates the two halves of the battery cell. The current state-of-the-art membrane is Nafion, which can be expensive to produce. The goal of this project is to create a membrane with characteristics that can rival those of Nafion but that can be produced using cheaper materials. Towards this end we are utilizing sodium silicate solutions to create flow battery membranes. Two main characteristics of these membranes were studied: 1) proton conductivity, which is essential to current flowing through the battery and 2) ion permeability, which dictates the rate at which the ions in the two halves of the battery cell mix and the battery quality deteriorates. Initial testing for proton conductivity revealed that the experimental membranes were performing within the same order of magnitude as Nafion. However, the experimental membranes showed high permeability relative to Nafion. Future work will focus on isolating variables that affect pore size and polydispersity in the synthesized membranes in order to size exclude redox ions from permeating the membrane while retaining effective proton conductivity.

Methylomicrobium buryatense 5GB1c is a strain of methanotrophic bacteria that serves as an attractive model for production of valuable compounds from methane that can be used in industrial applications. Using this bacteria to transform cheap methane into a commercial commodity is not only a profitable venture, but an effective use of this potent greenhouse gas. This project attempted to genetically manipulate 5GB1 to increase its concentration of cellular lipids, which can be used as precursors to diesel, and introduce new metabolic pathways to produce three stereoisomers of 2,3-butanediol, a compound that can be used in the synthesis of materials such as rubber, plastics, and several others. 5GB1 has a complex membrane structure to support methane oxidation, from which the desired lipids can be utilized in fuel production. By overexpressing five genes previously determined to be involved in high-lipid generating conditions, we expected a greater yield of the product. To accomplish this, direct chromosomal insertion of a genetic construct with a highly active promoter increased transcription of the target genes. After this successful transformation of the cells through homologous recombination, sample cultures were analyzed to determine if the level of lipid production increased. A knockout of the cell-shape determining gene was also made in an attempt to increase lipid concentration; however it was lethal. For 2,3-butanediol biosynthesis, cells were transformed with plasmid constructs containing genes encoding enzymes that are downstream of existing pathways within 5GB1. Three different sets of plasmids were made for the three stereoisomers of the compound, resulting in the production of mostly pure diols. After transformation, 5GB1 was expected to be able to convert methane to the desired products. This process can be scaled up at the industrial level for manufacture and profit.

A pressing issue for much of the world is finding energy resources alternative to fossil fuels. I conducted a literature review through databases such as JSTOR and ERIC that addresses fractal kinetics to describe the saccharification of lignocellulose. Lignocellulose is one of the most abundant biomass resources on earth found in plants and can be converted into a biofuel, ethanol. The process of converting lignocellulose to ethanol is similar to the process of converting starch, found in corn, into ethanol. In both processes the substrates go through saccharification, a procedure where they are broken down into glucose. The glucose is then fermented and is converted into ethanol chemicals. However, converting lignocellulose to ethanol has a very low conversion rate which inhibits the ability to use lignocellulose as a viable energy alternative. Primarily, the classical kinetics model is used to describe the saccharification of cellulose. Before the introduction of fractal geometry in the 1970s, the geometry of nature was considered too complex and irregular to describe analytically using Euclidean geometry. Since then, fractal geometry has been found to model natural phenomena. Fractal theory is important to helping scientists understand the saccharification of lignocellulose and develop models for efficient conversion in the future. With a consistent method to converting lignocellulose into a biofuel, society can move away from fossil fuels as our greatest energy source.

 Diabetes affects about 10% of the US population and is the 7th leading cause of death. Diabetes results from either a lack of insulin production (Type 1) or resistance to it (Type 2). The active form of insulin is a 51 amino acid monomer which regulates homeostasis of blood-glucose levels. It is crucial for insulin to be structurally sound and not degraded, especially for people using insulin pumps. However, insulin has a shelf life of about 28 days unopened and only 14 days after opening the container. Efforts to improve the stability of insulin may facilitate the development of implantable pump technologies for insulin delivery and allow for longer storage of insulin. Based on a review of the literature, I hypothesize that solvation in an Ionic Liquid solution will decrease the degradation and increase the shelf-life of insulin. To better understand the stability of the insulin protein, I compared its activity at an air-water interface to an air-ionic liquid interface. The approach consists of modeling the structure of insulin using the simulation software GROMACS and PLUMED. 10 nanosecond trials in different air-liquid interfaces were then analyzed to optimize the best insulin backbone stability. The goal is to extrapolate an ammonium- or imidazolium-based ionic liquid solution that will decrease the aggregation of the insulin monomers. Compared to the bulk insulin form, we found that the ionic liquid-protein solution demonstrates a lower radius of gyration and a root-mean-square deviation value that levels out towards 1 Angstrom representing a stable protein. These results are also supported by a decreased hydrodynamic radius and an increased free energy of unfolding the insulin protein. These findings suggest that insulin in an ionic liquid solution will last longer in vitro than in a water-based solution.

Conjugated polymer semiconductors have received substantial attention for providing a path to low cost manufacturing of electronics such as organic field-effect transistors, light emitting diodes, and solar cells. This work explores the electronic and structural effects of doping colloidal poly(3-hexlythiophene) (P3HT) nanofibers in non-aqueous solution. Doping injects charge carriers into the organic semiconductor and allows for modulation of electrical and optical properties. In solution, increasing dopant concentration also typically leads to uncontrolled polymer aggregation. In this work, we will demonstrate that doping and colloidal stability can be obtained for self-assembled P3HT nanofibers. This work characterizes the conductivity, structure, and optical properties of P3HT nanofibers as a function of dopant concentration and dopant molecular structure. These findings contribute to improved development of transparent thin films for organic electronics by achieving both solution stability and increased conductivity.

Ultraviolet photodetectors have wide-ranging applications, including use for missile detection. Current devices employ indium tin oxide (ITO), making them rigid and fragile. Development of flexible organic devices is therefore desirable to make more adaptable photodetectors. This set of experiments focuses on optimization of the polymer active layer in flexible organic ultraviolet photodetectors. Controlling thickness and morphology of the active layer is key to improving device performance. The active layer consists of an electron donor, a polymer called F8T2, and an electron acceptor, PC71BM. Optimization in this set of experiments is achieved through variation of preparation conditions, most notably the solvent used in processing. Other parameters varied include molecular weight of polymer, and ratio of electron donor to acceptor. Analysis of resulting films is performed in several ways. UV/Vis-spectroscopy provides information about morphology, while atomic force microscopy (AFM) allows for surface imaging of films on the nanoscale. Profilometry provides measurements of thickness. These forms of analysis reveal which preparation conditions should be used for fabrication of devices. Initial profilometry data suggests that processing with a dichlorobenzene/chloroform mix as a solvent results in films with roughly twice the thickness of films processed using pure dichlorobenzene. Acquisition of more data will drive future experiments on preparation conditions, allowing for optimization of active film thickness/morphology, and thereby device performance. This will allow for production of a more flexible and reliable form of ultraviolet photodetector.

The ability to recapitulate the dynamic presentation of signals in a stem cell’s microenvironment remains a major hurdle in tissue engineering. Controlling cell growth and differentiation in 4 dimensions (i.e., time and 3D space) would allow for heterogeneous synthetic tissues to be produced that match the complexity of their native counterparts. Combining strategies in both light-programmable hydrogels and recombinant protein engineering, we control the cellular microenvironment using proteins site-specifically modified with a bioorthogonal handle and able to covalently bind to a photocaged reactive group in the hydrogel. Previously we’ve demonstrated the ability to photopattern gels with fluorescent proteins that excite at different wavelengths, and have shown that multiple proteins can be patterned independently within the same material with 4D control. These techniques have many potential applications, including improving joint replacement. Current joint replacement therapies often involve use of metals, plastics, and ceramics, and commonly require future revision surgeries. We propose that through our techniques, we can generate a patterned bone/cartilage interface to improve joint replacement, creating a longer-term option for joint replacement. Towards this, we have generated two photopatternable recombinant growth factors, BMP-2 (bone morphogenic protein 2) and TGF-β (transforming growth factor β), known to direct human mesenchymal stem cell (hMSC) osteogenesis and chondrogenesis. I will encapsulate hMSCs in a hydrogel and direct cell differentiation and growth in 4D using a combination of photopatterned BMP-2 and TGF-β proteins. This research will have significant impact in tissue engineering, as it will enable recreation of complex physiological structures, grown outside the body with the patient’s own cells, that can be used for personalized medicine. Our approach is unique in that it allows for unprecedented control over microscale tissue structures, ultimately matching the complexity of native tissue.

In the United States, kidney failure (end stage renal disease/ ESRD) affects more than 871,000 people and costs over 40 billion dollars for treatment. The majority of these ESRD patients can sustain their lives via dialysis, which requires blood access. Synthetic vascular grafts are one way of creating the access, but they oftentimes fail within the first two years, in part due to the lack of endothelial ingrowth into the vessel walls. Our lab is developing a synthetic vascular graft that rivals the performance of native blood vessels by promoting complete healing of native vessels (e.g. endothelial cells) into the graft. This pro-healing effect is made possible by a precision-engineered microporous structure. However, due to this device’s porous properties, a sealant is required to prevent bleeding (hemorrhage). In order to simultaneously prevent hemorrhages and promote endothelial in-growth during the healing process, I have engineered a series of cross-linked gelatin with tunable biodegradability, mechanical properties, and low toxicity. In particular, cross-linkers genipin and EDC/NHS were explored. The shear strength of the hydrogel was examined by coating the luminal surface of the graft with the gelatin, incorporating this model into a flow regime, and analyzing the resulting surface effects with Scanning Electron Microscopy (SEM). Toxicity was analyzed through mice fibroblast seeding on a cross-linked hydrogel, and biodegradability was estimated by soaking the gelatin in a polyphenylene sulfide (PPS) buffer solution (with a physiological pH of 7.4) and measuring the resulting Young’s modulus with a universal testing machine (UTM). While lower crosslinking densities have rendered a more rapid remodeling by the body, higher crosslinking densities tend to display more durable mechanical properties; the crosslinking density was optimized based on these trends, such that the gelatin can effectively prevent initial bleeding while maintaining the biodegradability to allow the native blood vessel to heal into.

Freshwater lakes are an important source of the greenhouse gas methane contributing around 6-16% of the total atmospheric methane budget. Methane oxidation in freshwater lakes is the result of different functional guilds of bacteria working together as opposed to just methanotrophs themselves. Microbial communities in methane-fed lake sediment microcosms have not only displayed a clear response to methane by methanotrophs, but also by non-methanotrophic methylotrophs. To obtain a better understanding of the interaction between methanotrophs and methylotrophs, we investigated the role of methanol as a key methane-derived carbon compound enabling stable co-culture formations between a non-methanotrophic methylotroph (Methylotenera mobilis JLW8) and a methanotroph (Methylobacter tundripaludum 31/32). Along with JLW8 wild type, we tested different mutants of Methylotenera with deletions in the methanol oxidation pathway; XoxF mutants 1170, 2048 and 48/70-9. By monitoring the populations of Methylobacter and Methylotenera in the co-cultures with the use of flow cytometry, we find evidence that methane-derived methanol is likely the growth substrate used by Methylotenera in the artificially created methane-fed microcosms. All co-cultures formed stable communities with the exception of the double mutant, which is unable to grow on methanol, indicating that methanol is the key methane-derived component in community establishment. The wild type and both single mutants established co-cultures in similar patterns resulting in somewhat equal distributions of Methylobacter and Methylotenera by the 4th week. Both single mutants, however, showed consistently higher abundances of Methylotenera in comparison to the wild type co-cultures. This data also suggests that both single mutants may be better at oxidizing methanol than the wild type although the mechanisms for this are still unclear. These results provide insight into the growing significance of methanol in facilitating the complex communities invovled in methane oxidation.

The conventional decaffeination processes consume a lot of energy and use many chemical solvents that can be harmful to both the environment and human health. Although there are four main methods of decaffeination, they all consume high amounts of energy and tend to degrade the taste of the decaffeinated coffee; some processes even use harmful chemicals such as methylene chloride. To address this problem, natural clay minerals are chosen as the adsorbents to extract caffeine from coffee beverages due to their unique micro and nano structures. Selective caffeine adsorption can be achieved by engineering the clay structures, including methods of interlayer spacing control, ion exchange, edge sites modification, secondary structure control, and structural polymerization. Three clay minerals have been tested, which are laponite, bentonite, and zeolite Y. For all three clay materials tested, they initially do not show any caffeine adsorption. However, with different engineering principles applied, different degrees of caffeine removal are achieved. The best result is 80% caffeine reduction after 2 minutes and 99.6% after 20 minutes in real coffee using 1 gram of clay per 100mL of coffee; this particular result was achieved through clay interlayer spacing control, secondary structure control, and structural polymerization of the bentonite clay. Moreover, with the HPLC analysis, the result showed that the material is fairly selective for the caffeine molecule, and during the decaffeinated coffee taste tests, most of the participants said that decaffeination with clay yield better taste coffee compared to conventional decaffeinated coffee. This new decaffeination process is much faster and versatile since it can reduce much of the caffeine in most of the beverages that contain caffeine in just a few minutes. Clay mineral structural engineering is a very promising technology for selectively removing caffeine molecules and has great potentials for the beverage industry.

Ionic liquids (ILs) are well known to cause a range of interesting effects on proteins and enzymes. However, there is still much to be done to understand the molecular scale mechanisms of these processes. Using molecular dynamics (MD), we have studied how several IL solutions change the structure and behavior of two short, model, Leucine-Lysine (LK) composed peptides at a hydrophobic interface. These peptides - LKalpha14 and LKbeta15 - have been researched extensively through experiment and simulations in water, but have not yet been examined when exposed to ILs. In our study we found that the two 50% 1-Butyl-3-methylimidazolium solutions we tested had a substantial effect on both the secondary structure and surface affinity of our peptides when compared to water. IL solutions reduced the adsorption affinity of both LKalpha14 and LKbeta15 for the interface, while also preventing LKbeta15 from forming extended beta sheet structures. In place of these beta sheet structures, we observed the formation of a L-alpha-like helix for lone LKbeta15 peptides at the interface. IL presence also had a subtle effect on LKalpha14’s strong alpha helical character, reducing it for interface bound peptides and increasing it for peptides in bulk solution. This work provides several new testable hypothesis about IL action on biomolecule structure that can be studied in detail using surface techniques such as sum frequency generation (SFG) spectroscopy.

 For a nanoparticle to efficiently penetrate within the brain microenvironment, it must avoid any steric limitation it would experience as it moves between cells, vessels, and extracellular matrix (ECM) components. The particle must avoid any adhesive interactions, via hydrogen bonding, hydrophobic interactions, or electrostatic interactions between the particle surface and a cell membrane, protein, or ECM component. Steric limitations are influenced by the brain’s volume fraction and the tortuosity. To maximize diffusion within the brain, it is important to have a bio-inert particle that will avoid adhesive interactions to accurately assess the steric limitations that occur due to changes in volume fraction and tortuosity. However, nanoparticles in the brain microenvironment are exposed to a 300 mM ion concentration in cerebral spinal fluid (CSF), which contains multiple divalent cations. Using dynamic light scattering, we sought to characterize nanoparticle size and surface charge in the presence of CSF as a function of particle size, surface chemistry, and exposure time. We demonstrate that the presence of these divalent cations can disrupt the electrostatic double layers that provide nanoparticle stability and prevent nanoparticle aggregation in the brain. Our results demonstrate that within one hour after exposure to physiological CSF, nanoparticles that are electrostatically stabilized begin to aggregate, increasing in hydrodynamic size and polydispersity. Nanoparticles that are sterically stabilized (i.e with polyethylene glycol) aggregated in the presence of CSF, but on a much slower time scale. This aggregation behavior may be one reason why nanoparticles that are otherwise stable tend to aggregate, and therefore do not penetrate, once in the brain microenvironment. Characterizing nanoparticle behavior in the brain can have significant implications for nanoparticle design for drug delivery to brain diseases.

Proteins are naturally-occurring biopolymers that are useful in a wide range of therapeutic and imaging applications. Though natural proteins are comprised of just 20 monomeric amino acids, they can be post-translationally decorated to introduce expanded chemical functionality. Though several techniques have been developed, the majority do not provide site-specific modification nor stoichiometric conjugation necessary to preserve protein bioactivity. Additionally, proteins functionalized through these methods have proven difficult to purify after modification, thereby limiting potential clinical and industrial applications. Sortase-Tag Expressed Protein Ligation (STEPL) is a protein functionalization/purification method that solves many of these problems. This method allows functional probes to be site-specifically conjugated onto a protein, while simultaneously separating modified and unmodified proteins. Though this technique has been successfully demonstrated in the DeForest lab, a remaining challenge is to increase yield during protein expression. In our group, we exploit several microbiology techniques to optimize this process. Bacterial strain identity, growth conditions, reaction temperature, and protein solubility have all been shown to influence protein expression. Using Green Fluorescent Protein (GFP), we found that the STEPL yield increased when conducted for 4 hours at 37°C versus overnight at 18°C. This was determined through mass spectrometry, which showed hydrolyzed proteins after prolonged reaction. For some difficult to express proteins, including growth factors, the STEPL protocol resulted in a negligible protein yield. Through experimenting with a dialysis refolding protocol, functional growth factor Bone Morphogenic Protein-2 was produced at dramatically increased yields. Furthermore, experimenting with E. coli growth and STEPL reaction conditions has resulted in increased yield for many different functionalized proteins. Although progress has been made in producing functionalized protein with the STEPL method, yield remains below that obtained through other methods. Further experimentation to improve the robustness and yield of the STEPL protocol will increase the availability of functionalized proteins in biotherapeutics.

Hydrogels have proven to be excellent 3D cell culture platforms, serving as frameworks for synthetic tissue substitutes. Though given the complexity of the native extracellular environment, control over mechanical and biochemical cues within hydrogels is important in mimicking the extracellular matrix (ECM), the dynamic framework about which cells function. We seek to provide spatiotemporal control over cell fate within hydrogels formed through photo-mediated oxime ligation, a novel approach to photopolymerization seldom interfering with biological species present in cell encapsulation. By conjugating a photo-cleavable ortho-nitro benzyl (NPPOC) functionality to an aminooxy group, this otherwise spontaneous reaction may be spatiotemporally regulated with UV light. Excitation of the aminooxy-NPPOC complex upon UV light exposure cleaves NPPOC, enabling aminooxy to undergo ligation with an aldehyde. We have demonstrated the successful synthesis of 4-arm poly(ethylene glycol) (PEG) molecules separately functionalized with benzaldehyde and aminooxy-NPPOC end-groups. We have additionally demonstrated hydrogel formation following UV light exposure to 4-arm PEG solutions of varying compositions, verifying photo-mediated oxime ligation’s viability as a photopolymerization strategy. Following gelation, photo-mediated oxime ligation may be extended towards the incorporation of biochemical ligands via 3-dimensionally patterning NPPOC-conjugated proteins. Combining control over hydrogel geometry and stiffness with protein patterning, this dynamic hydrogel platform will expectedly aid in better understanding cell behavior through emulating the ECM’s heterogeneity. Consequently, an improved understanding of cell-matrix interactions may aid in advancing synthetic tissue substitutes.

The period of time before, during, and after birth (the perinatal period) is associated with the greatest risk of permanent brain injury, due in large part to perinatal asphyxia, where newborn infants suffer lack of oxygen and blood flow to the brain. Unfortunately, perinatal asphyxia, which can cause a hypoxic-ischemic insult (HI), is difficult to prevent or predict, and rates of perinatal asphyxia have remained around 2-4 per 1,000 live births, despite excellent obstetric care. Currently, therapeutic hypothermia (TH) is the only treatment that has been shown to provide robust improvement in newborns after moderate or severe perinatal asphyxia. Unfortunately, TH is not universally neuroprotective, and more effective therapeutic methods are necessary to reduce mortality and lead to symptom free survival of newborns with brain injury. In this study, we develop a curcumin-loaded poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticle for treatment of newborn HI. Currently, we are synthesizing the nanoparticles and doing characterization tests to determine if certain parameters are within the desired ranges. After this procedure, we will continue on and measure the drug loading and release of the nanoparticle. The results of this study are important because this nanoparticle has the ability to achieve high loading, sustained release of curcumin, and rapid diffusion within the brain microenvironment. Curcumin has recently been shown to prevent reduction of omega 3 fatty acids, which are critical to brain function and recovery after injury, particularly in the newborn brain after an HI event. Enhanced delivery of curcumin to the brain via a nanoparticle platform can have significant implications for treatment of HI in the newborn brain.