Dissolvable microarray patches of levodopa and carbidopa for Parkinson’s disease management

Carbidopa and levodopa remain the established therapeutic standard for managing Parkinson’s disease. Nevertheless, their oral administration is hindered by rapid enzymatic degradation and gastrointestinal issues, limiting their efficacy, and necessitating alternative delivery methods. This work presents a novel strategy employing dissolving microarray patches (MAPs) loaded with carbidopa and levodopa, formulated with Tween® 80 to improve their transdermal delivery. The fabricated MAPs demonstrated an acceptable mechanical strength, resisting pressures equivalent to manual human thumb application (32 N) onto the skin. Additionally, these MAPs exhibited an insertion depth of up to 650 µm into excised neonatal porcine skin. Ex vivo dermatokinetic studies could achieve delivery efficiencies of approximately 53.35 % for levodopa and 40.14 % for carbidopa over 24 h, demonstrating their significant potential in drug delivery. Biocompatibility assessments conducted on human dermal fibroblast cells corroborated acceptable cytocompatibility, confirming the suitability of these MAPs for dermal application. In conclusion, dissolving MAPs incorporating carbidopa and levodopa represent a promising alternative for improving the therapeutic management of Parkinson’s disease.<br/

BCC-CSM2-HR: a high-resolution version of the Beijing Climate Center Climate System Model

International audienceBCC-CSM2-HR is a high-resolution version of the Beijing Climate Center (BCC) Climate System Model (T266 in the atmosphere and 1/4∘ latitude × 1/4∘ longitude in the ocean). Its development is on the basis of the medium-resolution version BCC-CSM2-MR (T106 in the atmosphere and 1∘ latitude × 1∘ longitude in the ocean) which is the baseline for BCC participation in the Coupled Model Intercomparison Project Phase 6 (CMIP6). This study documents the high-resolution model, highlights major improvements in the representation of atmospheric dynamical core and physical processes. BCC-CSM2-HR is evaluated for historical climate simulations from 1950 to 2014, performed under CMIP6-prescribed historical forcing, in comparison with its previous medium-resolution version BCC-CSM2-MR. Observed global warming trends of surface air temperature from 1950 to 2014 are well captured by both BCC-CSM2-MR and BCC-CSM2-HR. Present-day basic atmospheric mean states during the period from 1995 to 2014 are then evaluated at global scale, followed by an assessment on climate variabilities in the tropics including the tropical cyclones (TCs), the El Niño–Southern Oscillation (ENSO), the Madden–Julian Oscillation (MJO), and the quasi-biennial oscillation (QBO) in the stratosphere. It is shown that BCC-CSM2-HR represents the global energy balance well and can realistically reproduce the main patterns of atmospheric temperature and wind, precipitation, land surface air temperature, and sea surface temperature (SST). It also improves the spatial patterns of sea ice and associated seasonal variations in both hemispheres. The bias of the double intertropical convergence zone (ITCZ), obvious in BCC-CSM2-MR, almost disappears in BCC-CSM2-HR. TC activity in the tropics is increased with resolution enhanced. The cycle of ENSO, the eastward propagative feature and convection intensity of MJO, and the downward propagation of QBO in BCC-CSM2-HR are all in a better agreement with observations than their counterparts in BCC-CSM2-MR. Some imperfections are, however, noted in BCC-CSM2-HR, such as the excessive cloudiness in the eastern basin of the tropical Pacific with cold SST biases and the insufficient number of tropical cyclones in the North Atlantic