Fu'cupping Physical Permeation-Enhancing Technique Enhances the Therapeutic Efficacy of Corydalis yanhusuo Gel Plaster.

Corydalis yanhusuo, a traditional Chinese medicine, is widely used to treat various pains, and its active ingredients are alkaloids. This study aimed to develop a new type of transdermal gel plaster containing the extract of C. yanhusuo. Studies have shown that Fu'cupping physical permeation-enhancing technique can promote the penetration of alkaloids and improve the efficacy of drugs. A transdermal gel plaster containing the extract of C. yanhusuo was prepared and optimized using an orthogonal experimental design. The skin permeation ability of the gel plaster was studied in vitro, while the anti-inflammatory and analgesic effects of the prepared patch alone or with Fu'cupping physical permeation-enhancing technique were evaluated in a rat model. The formulation of a gel plaster containing C. yanhusuo extract was successfully prepared with an optimized composition consisting of glycerin (15 g), sodium polyacrylate (2 g), silicon dioxide (0.3 g), ethanol (2 g), aluminum oxide (0.1 g), citric acid (0.05 g), the C. yanhusuo extract (3 g), and water (15 g). The cumulative transdermal permeation of dehydrocorydaline, corypalmine, tetrahydropalmatine, and corydaline in 24 h was estimated to be 569.7 ± 63.2, 74.5 ± 13.7, 82.4 ± 17.2, and 38.9 ± 8.1 µg/cm2, respectively. The in vitro diffusion of dehydrocorydaline and corydaline followed the zero-order kinetics profile, while that of corypalmine and tetrahydropalmatine followed a Higuchi equation. The prepared gel plaster significantly reduced paw swelling, downregulated inflammatory cytokines, and mitigated pain induced by mechanical or chemical stimuli. The Fu'cupping physical permeation-enhancing technique further improved the anti-inflammatory and analgesic effects of the patch. The combined application of the Fu'cupping physical permeation-enhancing technique and the alkaloid gel plaster may be effective against inflammation and pain.

Glomerulus-Targeted ROS-Responsive Polymeric Nanoparticles for Effective Membranous Nephropathy Therapy.

Membranous nephropathy (MN) is a common immune-mediated glomerular disease that requires the development of safe and highly effective therapies. Celastrol (CLT) has shown promise as a therapeutic molecule candidate, but its clinical use is currently limited due to off-target toxicity. Given that excess levels of reactive oxygen species (ROS) contributing to podocyte damage is a key driver of MN progression to end-stage renal disease, we rationally designed ROS-responsive cationic polymeric nanoparticles (PPS-CPNs) with a well-defined particle size and surface charge by employing poly(propylene sulfide)-polyethylene glycol (PPS-PEG) and poly(propylene sulfide)-polyethylenimine (PPS-PEI) to selectively deliver CLT to the damaged glomerulus for MN therapy. Experimental results show that PPS-CPNs successfully crossed the fenestrated endothelium, accumulated in the glomerular basement membrane (GBM), and were internalized by podocytes where rapid drug release was triggered by the overproduction of ROS, thereby outperforming nonresponsive CLT nanotherapy to alleviate subepithelial immune deposits, podocyte foot process effacement, and GBM expansion in a rat MN model. Moreover, the ROS-responsive CLT nanotherapy was associated with significantly lower toxicity to major organs than free CLT. These results suggest that encapsulating CLT into PPS-CPNs can improve efficacy and reduce toxicity as a promising treatment option for MN.

Amorphous solid dispersions of lidocaine and lidocaine HCl produced by ball milling with well-defined RAFT-synthesised methacrylic acid polymers.

This study focuses on the use of methacrylic acid polymers synthesised via the Reversible Addition Fragmentation chain Transfer (RAFT) polymerisation method for the production of amorphous solid dispersions (ASDs) by ball milling, to kinetically solubilize a poorly water-soluble model drug. The solid-state characteristics and the physical stability of the formulations were investigated using X-ray diffraction, differential scanning calorimetry, and infrared spectroscopy. This was followed by dissolution studies in different media. It was discovered that the acidic polymers of methacrylic acid were capable of interacting with the weakly basic drug lidocaine and its hydrochloride salt form to produce ASDs when a polymer to drug ratio of 70:30 w/w was used. The ASDs remained amorphous following storage under accelerated aging conditions (40 °C and 75% relative humidity) over 8 months. Fast dissolution and increased lidocaine solubility in different media were obtained from the ASDs owing to the reduced microenvironment pH and enhanced solubilization of the drug caused by the presence of the acidic polymer in the formulation. Production of ASDs using well-defined RAFT-synthesised acidic polymers is a promising formulation strategy to enhance the pharmaceutical properties of basic poorly water-soluble drugs.

Comparison of COVID-19 and Lung Cancer via Reactive Oxygen Species Signaling.

COVID-19 and lung cancer are two severe pulmonary diseases that cause millions of deaths globally each year. Understanding the dysregulated signaling pathways between them can benefit treating the related patients. Recent studies suggest the critical role of reactive oxygen species (ROS) in both diseases, indicating an interplay between them. Here we reviewed references showing that ROS and ROS-associated signaling pathways, specifically via NRF2, HIF-1, and Nf-κB pathways, may bridge mutual impact between COVID-19 and lung cancer. As expected, typical ROS-associated inflammation pathways (HIF-1 and Nf-κB) are activated in both diseases. The activation of both pathways in immune cells leads to an overloading immune response and exacerbates inflammation in COVID-19. In lung cancer, HIF-1 activation facilitates immune escape, while Nf-κB activation in T cells suppresses tumor growth. However, the altered NRF2 pathway show opposite trends between them, NRF2 pathways exert immunosuppressive effects in both diseases, as it represses the immune response in COVID-19 patients while facilitates the immune escape of tumor cells. Furthermore, we summarized the therapeutic targets (e.g., phytochemicals) on these ROS pathways. In sum, our review focus on the understanding of ROS Signaling in COVID-19 and lung cancer, showing that modulating ROS signaling pathways may alleviate the potentially mutual impacts between COVID-19 and lung cancer patients.