Mukundpura is a carbonaceous chondrite (CM2) recently fell in Rajasthan, India (June 6, 2017). A typical finegrained, clast-dominant matrix contains a few isolated forsterite and FeO-rich olivine grains. In this study, forsterite-rich olivines were investigated using color cathodoluminescence (CL) and Raman spectroscopy in order to explain the primitive stages of asteroidal aqueous alteration. Isolated forsterite (Fo 99) in Mukundpura emits bright CL of varying color and shows CL zonation in different patterns accounting the structural defects and chemical inhomogeneity. Blue luminescence (also distinguished by enriched CaO and TiO 2) is common in cores of the relict forsterite attributing refractory nature of the olivine. Electron Probe Micro Analyzer (EPMA) line scan across the CL-active forsterite grains shows minor elements zonation especially for activator elements and thus provides a correlation of color of the emitted luminescence with diffusible ions. The red CL zonation (also characterized by enriched FeO, Cr 2 O 3 , and MnO content) is common along the majority of forsterite rims suggesting aqueous activity in the parent asteroid. The strongest doublet Raman peaks corresponding to 821 and 854 cm −1 are due to SiO 4 tetrahedral vibrational modes, and other peaks are often related to infer pure crystalline state of the forsterite. Thus, a combination of CL imaging and Raman spectroscopy is useful to explain the chemical-structural properties of luminescent pure forsterite and also helps in understanding the aqueous alteration of CM chondrite.
The down-regulation of genes directly involved in the pathogenesis of severe lung diseases through siRNA delivery to the lung has gained recently tremendous research interest. Nevertheless, adequately engineered inhalable siRNA formulations are required to translate this approach in vivo. Here, we propose novel hybrid lipid/polymer hybrid nanoparticles (hNPs) for pulmonary siRNA delivery consisting of a poly(lactic-co-glycolic) acid (PLGA) core surrounded by a dipalmitoyl phosphatidylcholine (DPPC) shell. A preliminary formulation study allowed to select optimized "muco-inert" PLGA/DPPC hNPs, comprising or not poly(ethylenimine) (PEI) as third component, which displayed mean hydrodynamic diameters of 150 nm, with a low polydispersity index (~0.1) and a negative zeta potential (~-25 mV). A combination of siRNA of interest for cystic fibrosis (CF), against α and β subunits of the sodium transepithelial channe,l was entrapped with high efficiency in optimised hNPs containing or not PEI. siRNA-loaded hNPs displayed a peculiar triphasic release lasting for 5 days, which slowed down in the presence of PEI. Both formulations showed optimal in vitro aerosol performance after delivery with a vibrating mesh nebulizer and in vitro long-term stability upon incubation with artificial CF mucus. The fate and the effects of hNPs upon aerosolization on a triple cell co-culture model (TCCC) mimicking human epithelial airway barrier were assessed. Cell uptake studies confirmed the ability of fluorescently labelled hNPs to be internalized inside cells of the epithelial airway barrier. As measured by lactate dehydrogenase (LDH) release 24 h after treatment, PLGA/DPPC hNPs did not exert any cytotoxic effect towards TCCC. Furthermore, TCCC exposure to PLGA/DPPC hNPs did not result in a significant increase of tumor necrosis factor (TNF)-alpha release after 24 h, suggesting no acute pro-inflammatory effect. Overall, results demonstrate the great potential of PLGA/DPPC hNPs as carriers for siRNA delivery on the human epithelial airway barrier, prompting towards investigation of their therapeutic effectiveness in CF.
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