Reactive Oxygen Species-Responsive Gel-Based Microneedle Patches for Prolonged and Intelligent Psoriasis Management

Abstract

Psoriasis is an inflammatory skin disease. Microneedle (MN) patches can improve psoriasis treatment outcomes by increasing local drug content in the skin. As psoriasis frequently relapses, developing intelligent MN-based drug delivery systems with prolonged therapeutic drug levels and improved treatment efficiency is of great significance. Here, we designed detachable H2O2-responsive gel-based MN patches containing methotrexate (MTX) and epigallocatechin gallate (EGCG) by using EGCG as both cross-linkers for needle-composited materials and anti-inflammatory drugs. The gel-based MNs had dual-mode drug release kinetics, which quickly released MTX diffusively and sustainably released EGCG in an H2O2-responsive way. Compared with dissolving MNs, the gel-based MNs extended skin retention of EGCG, leading to prolonged reactive oxygen species (ROS) scavenging effects. The ROS-responsive MN patches that transdermally delivered antiproliferative and anti-inflammatory drugs improved treatment outcomes in both psoriasis-like and prophylactic psoriasis-like animal models.

Engineering MMP-2 Activated Nanoparticles Carrying B7-H3 Bispecific Antibodies for Ferroptosis-Enhanced Glioblastoma Immunotherapy

“…From this point, S-biAb/dEGCG@NPs displayed similar dEGCG release results as biAbs, with values 4.1-fold higher than that of the MMP-2-insensitive nanoparticles (Figure S12). The excellent binding of EGCG to various bioactive molecules is achieved via hydrophobic and electrostatic interactions. , Nonionic reagents, such as Tween 20 and Triton X-100, induce the dissociation of S-biAb/dEGCG@NPs. In contrast, NaCl and urea, as ionic reagents, have almost no impact on them, suggesting that dEGCG exhibits the inherent binding of EGCG to bioactive molecules via hydrophobic interactions (Figure d).…”

“…23,24 Its anticancer effect is mainly attributed to its production of intracellular ROS and the subsequent induction of oxidative damage to biomolecules such as proteins, lipids, and DNA. 25 Thus, it will be interesting to investigate whether the production of ROS induced by EGCG may be combined with B7-H3-based immunotherapy to enhance the anti-GBM effect.…”

“…Ferroptosis, a form of regulated cell death, is characterized morphologically by smaller mitochondria, condensed mitochondrial membrane densities, decrease in or disappearance of the mitochondrial cristae, and rupture of the outer mitochondrial membrane, which are driven by deactivation of the lipid glutathione peroxidase 4 (GPX4) and subsequent accumulation of lipid peroxide and reactive oxygen species (ROS). − A recent study by Wang et al demonstrated that interferon-γ (IFN-γ) secreted by tumor-infiltrating lymphocytes (TILs) can kill cancer cells by ferroptosis and is involved in the downregulation of the expression levels of solute carrier family 3 member 2 (SLC3A2) and solute carrier family 7 member 11 (SLC7A11) . Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, has been shown to possess beneficial properties, including anti-inflammatory, anticancer, antiangiogenic, antioxidant, neuroprotective, and DNA-protective effects. , Its anticancer effect is mainly attributed to its production of intracellular ROS and the subsequent induction of oxidative damage to biomolecules such as proteins, lipids, and DNA . Thus, it will be interesting to investigate whether the production of ROS induced by EGCG may be combined with B7-H3-based immunotherapy to enhance the anti-GBM effect.…”

A Novel Methacryloyl Chitosan Hydrogel Microneedles Patch with Sustainable Drug Release Property for Effective Treatment of Psoriasis

“…Subsequently, the Franz diffusion cell was placed on a transdermal diffusion apparatus (37 °C, 200 rpm). 300 μL receiving solutions were taken at specific time points (2,4,6,8,10,12,16,20, and 24 h) as the sample solution to be tested and immediately replenished with 300 μL of PBS (pH 7.4). Three parallel samples were made in each group.…”

“…Psoriasis is an immune-mediated chronic inflammatory skin disease, which affects 125 million people worldwide. [1,2] Psoriasis has a high recurrent and low cure rate, which not only increases the economic pressure on families and society, but also induces a variety of complications that seriously threaten the lives of patients. [3,4] Topical transdermal drug delivery is a common mode of drug delivery for psoriasis treatment.…”