A Neolithic innovation in eastern Arabia: haematite axes and adzes

International audienceWell before metallurgy, Neolithic societies in the Gulf were engaging in a very peculiar form of metal object production, particularly of axes and adzes made from haematite. In the heart of the Neolithic Middle East, this innovation was specific to Arabian shores between the Musandam and Qatar peninsulas. Quite infrequent among Neolithic lithic assemblages from Arabia, axes and adzes were mostly collected on the surface of domestic settlements. One is often dealing with objects to which the most focus has been given, apart from arrowheads and projectile points. Several sites or outcrops are present on the Emirati coastline and Gulf islands. Inland mountain ranges also include some of these. From Ra’s al‐Khaimah to Qatar, only 500 km separate the most distant Neolithic domestic settlements which possess haematite axes or hoes, a distance that is quite small when one considers the circulation of polished stone blades in other societies of the same period. Within the Middle East, south‐eastern Arabia during the Neolithic engaged in a very original means of production of metal objects, as the latter did not focus on copper, a very malleable and much more available material, but on haematite, which was much harder

Pulmonary Delivery of Voriconazole Loaded Nanoparticles Providing a Prolonged Drug Level in Lungs: A Promise for Treating Fungal Infection

Current therapies are insufficient to prevent recurrent fungal infection especially in the lower part of the lung. A careful and systematic understanding of the properties of nanoparticles plays a significant role in the design,development, optimization, and in vivo performances of the nanoparticles. In the present study, PLGA nanoparticles containing the antifungal drug voriconazole was prepared and two best formulations were selected for further characterization and in vivo studies. The nanoparticles and the free drug were radiolabeled with technetium-99m with 90% labelling efficiency, and the radiolabeled particles were administered to investigate the effect on their blood clearance, biodistribution, and in vivo gamma imaging. In vivo deposition of the drug in the lobes of the lung was studied by LC−MS/MS study. The particles were found to be spherical and had an average hydrodynamic diameter of 300 nm with a smooth surface. The radiolabeled particles and the free drug were found to accumulate in various major organs. Drug accumulation was more pronounced in the lung in the case of administration of the nanoparticles than that of the free drug. The free drug was found to be excreted more rapidly than the nanoparticle containing drug following the inhalation route as assessed by gamma scintigraphy study. Thus, the study reveals that pulmonary administration of nanoparticles containing voriconazole could be a better therapeutic choice even as compared to the iv route of administration of the free drug and/or the drug loaded nanoparticles

Distribution and Cellular Uptake of PEGylated Polymeric Particles in the Lung Towards Cell-Specific Targeted Delivery

PURPOSE: We evaluated the role of a poly(ethylene glycol) (PEG) surface coating to increase residence times and alter the cellular fate of nano- and microparticles delivered to the lung. METHODS: Three sizes of PRINT hydrogel particles (80×320 nm, 1.5 and 6 um donuts) with and without a surface PEG coating were instilled in the airways of C57/b6 mice. At time points of 1, 7, and 28 days, BALF and whole lungs were evaluated for the inflammatory cytokine Il-6 and chemokine MIP-2, histopathology, cellular populations of macrophages, dendritic cells (DCs), and granulocytes, and particulate uptake within these cells through flow cytometry, ELISAs, and fluorescent imaging. RESULTS: Particles of all sizes and surface chemistries were readily observed in the lung with minimal inflammatory response at all time points. Surface modification with PEGylation was found to significantly increase lung residence times and homogeneous lung distribution, delaying macrophage clearance of all sizes, with the largest increase in residence time observed for 80×320 nm particles. Additionally, it was observed that DCs were recruited to the airway following administration of unPEGylated particles and preferentially associated with these particles. CONCLUSIONS: Pulmonary drug delivery vehicles designed with a PEG surface coating can be used to delay particle uptake and promote cell-specific targeting of therapeutics