Nanotechnology-Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

The appearance and rapid spread of drug resistant strains of tuberculosis (TB), one of the deadliest infectious diseases, pose a serious threat to public health and increase the need for shorter, less toxic, and more effective therapies. Developing new drugs is difficult and often associated with side effects, so nanotechnology has emerged as a tool to improve current treatments and to rescue drugs having elevated toxicity or poor solubility. Due to their size and surface chemistry, antimicrobial-loaded nanocarriers are avidly taken up by macrophages, the main cells hostingMycobacterium tuberculosis. Macrophages are continuously recruited to infected areas, they can transport drugs with them, making passive targeting a good strategy for TB treatment. Active targeting (decorating surface of nanocarriers with ligands specific to receptors displayed by macrophages) further increases local drug concentration, and thus treatment efficacy. Although in in vivo studies, nanocarriers are often administered intravenously in order to avoid inaccurate dosage in animals, translation to humans requires more convenient routes like pulmonary or oral administration. This report highlights the importance and progress of pulmonary administration, passive and active targeting strategies toward bacteria reservoirs to overcome the challenges in TB treatment

Paleogeographic evolution of the Southern Pannonian Basin: 40Ar/39Ar age constraints on the Miocene continental series of notthern Croatia

The Pannonian Basin, originating during the Early Miocene, is a large extensional basin incorporated between Alpine, Carpathian and Dinaride fold-thrust belts. Back-arc extensional tectonics triggered deposition of up to 500-m-thick continental fluvio-lacustrine deposits distributed in numerous sub-basins of the Southern Pannonian Basin. Extensive andesitic and dacitic volcanism accompanied the syn-rift deposition and caused a number of pyroclastic intercalations. Here, we analyze two volcanic ash layers located at the base and top of the continental series. The lowermost ash from Mt. Kalnik yielded an 40Ar/39Ar age of 18.07 ± 0.07 Ma. This indicates that the marine-continental transition in the Slovenia-Zagorje Basin, coinciding with the onset of rifting tectonics in the Southern Pannonian Basin, occurs roughly at the Eggenburgian/ Ottnangian boundary of the regional Paratethys time scale. This age proves the synchronicity of initial rifting in the Southern Pannonian Basin with the beginning of sedimentation in the Dinaride Lake System. Beside geodynamic evolution, the two regions also share a biotic evolutionary history: both belong to the same ecoregion, which we designate here as the Illyrian Bioprovince. The youngest volcanic ash level is sampled at the Glina and Karlovac sub-depressions, and both sites yield the same 40Ar/39Ar age of 15.91 ± 0.06 and 16.03 ± 0.06 Ma, respectively. This indicates that lacustrine sedimentation in the Southern Pannonian Basin continued at least until the earliest Badenian. The present results provide not only important bench marks on duration of initial synrift in the Pannonian Basin System, but also deliver substantial backbone data for paleogeographic reconstructions in Central and Southeastern Europe around the Early–Middle Miocene transition