Projected changes of wintertime synoptic‐scale transient eddy activities in the East Asian eddy‐driven jet from CMIP5 experiments

The wintertime East Asian eddy‐driven jet (EAEJ) responding to climate change in the 21st century is studied using model outputs from the Coupled Model Intercomparison Project phase 5 (CMIP5). Compared to the location displacement in oceanic eddy‐driven jets, the magnitude change of synoptic‐scale transient eddy activities, measured by eddy kinetic energy (EKE), is a more striking feature in EAEJ. An intensified EKE is projected unanimously by CMIP5 models, suggesting that potential strong winter storm events are likely to happen in East Asian midlatitude in a warming climate. The future change of EKE in EAEJ can be understood in terms of growing baroclinicity wave. The upper level EKE is highly correlated to the low‐level static stability, Brunt‐Väisälä frequency (BVF). CMIP5 models generally project an intensified upper evel EKE with a reduced low‐level BVF (ΔEKE ∝ −ΔBVF). Meanwhile, the enhancement of EKE is also constrained by its historical state (ΔEKE ∝ −EKE). Intermodel variabilities among CMIP5 models reveal a similar but weaker relationship between ΔBVF (or EKE) and ΔEKE, indicating relatively large model diversities and independencies among CMIP5 models.Key PointsThe East Asian eddy‐driven jet will be intensified in a warming climateThe enhancement is related to the surface stability and the historical stateCMIP5 models exhibit large model diversities and independenciesPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113168/1/grl53203.pd

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/

Poly(acrylic acid)/poly(vinyl alcohol) microarray patches for continuous transdermal delivery of levodopa and carbidopa: in vitro and in vivo studies

Levodopa (LD) has been the most efficacious medication and the gold standard therapy for Parkinson’s disease (PD) for decades. However, its long-term administration is usually associated with motor complications, which are believed to be the result of the fluctuating pharmacokinetics of LD following oral administration. Duodopa® is the current option to offer a continuous delivery of LD and its decarboxylase inhibitor carbidopa (CD); however, its administration involves invasive surgical procedures, which could potentially lead to lifelong complications, such as infection. Recently, dissolving microarray patches (MAPs) have come to the fore as an alternative that can bypass the oral administration route in a minimally invasive way. This work explored the potential of using dissolving MAPs to deliver LD and CD across the skin. An acidic polymer poly(acrylic acid) (PAA) was used in the MAP fabrication to prevent the potential oxidation of LD at neutral pH. The drug contents of LD and CD in the formulated dissolving MAPs were 1.82 ± 0.24 and 0.47 ± 0.04 mg/patch, respectively. The in vivo pharmacokinetic study using female Sprague–Dawley® rats (Envigo RMS Holding Corp, Bicester, UK) demonstrated a simultaneous delivery of LD and CD and comparable AUC values between the dissolving MAPs and the oral LD/CD suspension. The relative bioavailability for the dissolving MAPs was calculated to be approximately 37.22%. Accordingly, this work highlights the use of dissolving MAPs as a minimally invasive approach which could potentially bypass the gastrointestinal pathway and deliver both drugs continuously without surgery

Dissolving microarray patches loaded with a rotigotine nanosuspension: a potential alternative to Neupro® patch

Parkinson's disease (PD), affecting about ten million people globally, presents a significant health challenge. Rotigotine (RTG), a dopamine agonist, is currently administered as a transdermal patch (Neupro®) for PD treatment, but the daily application can be burdensome and cause skin irritation. This study introduces a combinatorial approach of dissolving microarray patch (MAP) and nanosuspension (NS) for the transdermal delivery of RTG, offering an alternative to Neupro®. The RTG-NS was formulated using a miniaturized media milling method, resulting in a nano-formulation with a mean particle size of 274.09 ± 7.43 nm, a PDI of 0.17 ± 0.04 and a zeta potential of −15.24 ± 2.86 mV. The in vitro dissolution study revealed an enhanced dissolution rate of the RTG-NS in comparison to the coarse RTG powder, under sink condition. The RTG-NS MAPs, containing a drug layer and a ‘drug-free’ supporting baseplate, have a drug content of 3.06 ± 0.15 mg/0.5 cm2 and demonstrated greater amount of drug delivered per unit area (∼0.52 mg/0.5 cm2) than Neupro® (∼0.20 mg/1 cm2) in an ex vivo Franz cell study using full-thickness neonatal porcine skin. The in vivo pharmacokinetic studies demonstrated that RTG-NS MAPs, though smaller (2 cm2 for dissolving MAPs and 6 cm2 for Neupro®), delivered drug levels comparable to Neupro®, indicating higher efficiency per unit area. This could potentially avoid unnecessarily high plasma levels after the next dose at 24 h, highlighting the benefits of dissolving MAPs over conventional transdermal patches in PD treatment.<br/