Development of a targeted and controlled nanoparticle delivery system for FoxO1 inhibitors

Background: Poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) are polymers approved by the United States’ Food and Drug Administration. Drugs for various medical treatments have been encapsulated in PLGA-PEG nanoparticles for targeted delivery and reduction of unwanted side effects. Methods: A flow synthesis method for PLGA-PEG nanoparticles containing FoxO1 inhibitors and adipose vasculature targeting agents was developed. A set of nanoparticles including PLGA and PLGA-PEG-P3 unloaded and drug loaded were generated. The particles were characterized by DLS, fluorescence spectroscopy, TEM, and dialysis. Endotoxin levels were measured using the LAL chromogenic assay. Our approach was compared to over 270 research articles using information extraction tools. Results: Nanoparticle hydrodynamic diameters ranged from 142.4 ±0.4 d.nm to 208.7 ±3.6 d.nm while the polydispersity index was less than 0.500 for all samples (0.057 ±0.021 to 0.369 ±0.038). Zeta potentials were all negative ranging from -4.33 mV to -13.4 mV. Stability testing confirmed that size remained unchanged for up to 4 weeks. For AS1842856, loading was 0.5 mg drug/mL solution and encapsulation efficiency was ~100%. Dialysis indicated burst release of drug in the first 4 hours. Conclusion: PLGA encapsulation of AS1842856 was successful but unsuccessful for the two more hydrophilic drugs. Alternative syntheses such as water/oil/water emulsion or liposomal encapsulation are being considered. Analysis of data from published papers on PLGA nanoparticles indicated that our results were consistent with identified process-structure relationships and few groups reported endotoxin levels even though in vivo testing was performed.https://scholarscompass.vcu.edu/gradposters/1071/thumbnail.jp

Approaching quantum anomalous Hall effect in proximity-coupled YIG/graphene/h-BN sandwich structure

Quantum anomalous Hall state is expected to emerge in Dirac electron systems such as graphene under both sufficiently strong exchange and spin-orbit interactions. In pristine graphene, neither interaction exists; however, both interactions can be acquired by coupling graphene to a magnetic insulator (MI) as revealed by the anomalous Hall effect. Here, we show enhanced magnetic proximity coupling by sandwiching graphene between a ferrimagnetic insulator yttrium iron garnet (YIG) and hexagonal-boron nitride (h-BN) which also serves as a top gate dielectric. By sweeping the top-gate voltage, we observe Fermi level-dependent anomalous Hall conductance. As the Dirac point is approached from both electron and hole sides, the anomalous Hall conductance reaches 1/4 of the quantum anomalous Hall conductance 2e2/h. The exchange coupling strength is determined to be as high as 27 meV from the transition temperature of the induced magnetic phase. YIG/graphene/h-BN is an excellent heterostructure for demonstrating proximity-induced interactions in two-dimensional electron systems

The effect of fog on the probability density distribution of the ranging data of imaging laser radar

This paper outlines theoretically investigations of the probability density distribution (PDD) of ranging data for the imaging laser radar (ILR) system operating at a wavelength of 905 nm under the fog condition. Based on the physical model of the reflected laser pulses from a standard Lambertian target, a theoretical approximate model of PDD of the ranging data is developed under different fog concentrations, which offer improved precision target ranging and imaging. An experimental test bed for the ILR system is developed and its performance is evaluated using a dedicated indoor atmospheric chamber under homogeneously controlled fog conditions. We show that the measured results are in good agreement with both the accurate and approximate models within a given margin of error of less than 1%

Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, prevents the development of murine systemic lupus erythematosus-like diseases in MRL/lpr autoimmune mice and BDF1 hybrid mice

INTRODUCTION: Naturally occurring CD4(+)CD25(+ )regulatory T (Treg) cells are central to the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells lead to systemic lupus erythematosus (SLE). Manipulating the number or activity of Treg cells is to be a promising strategy in treating it and other autoimmune diseases. We have examined the effects of Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, on SLE-like symptoms in MRL/lpr autoimmune mice and BDF1 hybrid mice. Whether the beneficial effect of Y27 involves modulation of CD4(+)CD25(+ )Treg cells has also been investigated. METHODS: Female MRL/lpr mice that spontaneously develop lupus were treated orally by gavage with Y27 for 10 weeks, starting at 10 weeks of age. BDF1 mice developed a chronic graft-versus-host disease (GVHD) by two weekly intravenous injections of parental female DBA/2 splenic lymphocytes, characterized by immunocomplex-mediated glomerulonephritis resembling SLE. Y27 was administered to chronic GVHD mice for 12 weeks. Nephritic symptoms were monitored and the percentage of CD4(+)CD25(+)FoxP3(+ )Treg peripheral blood leukocyte was detected with mouse regulatory T cell staining kit by flowcytometry. Purified CD4(+)CD25(+ )Tregs were assessed for immune suppressive activity using the mixed lymphocyte reaction. RESULTS: The life-span of MRL/lpr mice treated with Y27 for 10 weeks was significantly prolonged, proteinuria and renal lesion severity were ameliorated, and blood urea nitrogen, triglyceride and serum anti-double-stranded DNA antibodies were decreased. Similar results were found in chronic GVHD mice. Administration of Y27 had little impact on percentage of the peripheral blood lymphocyte CD4(+)CD25(+)Foxp3(+ )Treg cells in both groups of mice. In contrast, the suppressive capacity of CD4(+)CD25(+ )Treg cells in splenocytes was markedly augmented in Y27-treated mice ex vivo. CONCLUSIONS: Experimental evidence of the protect effects of Y27 against autoimmune nephritis has been shown. The mechanism may involve enhancement of the suppressive capacity of CD4(+)CD25(+ )Treg cells