Matrine-loaded self-adhesive swelling microneedle for inflammation regulation to improve eczema treatment

Eczema is a common chronic dermatological disease.Conventional treatments exhibit limited efficacy due to fast drug release resulting in short-term relief.Development of a new treatment strategy that enables sustained drug release and longterm maintenance on the skin surface is necessary.A self-adhesive swelling microneedle patch(SDSMNs)was designed and constructed using a two-step casting method.The adhesive substrate was prepared by blending gelatin and dopamine via oxidation of NaIO4,so it could adhere onto the skin surface as well as withstand repeated bending movement without detachment.The swelling needles were fabricated using polyvinyl alcohol(PVA)and polyvinylpyrrolidone(PVP),which could swell by absorbing interstitial fluid and release the drug in a controlled manner.SDSMNs also showed desirable antibacterial activities toward E.coli and S.aureus.The adhesive microneedles loaded with matrine(MAT-SDSMNs),an antiinflammatory Chinese medicine,dramatically relieved eczema symptoms through IL-17 mediated inflammation responses.The use of MAT-SDSMNs significantly decreased the infiltration of inflammation cells and level of inflammatory cytokines,reduced the skin thickness,and increased collagen deposition fraction compared with conventional ointment or subcutaneous injection.The results suggested that MAT-SDSMNs can improve eczema treatment by regulating the local inflammatory microenvironment,providing a simple,self-administered sustainable strategy for eczema treatment.

Effect of sodium alginate-based hydrogel loaded with lutein on gut microbiota and inflammatory response in DSS-induced colitis mice

In order to effectively deliver lutein to the inflamed colon and better exert its pharmacological activity,this paper constructed a sodium alginate hydrogel-based delivery system loaded with lutein nanoparticles,evaluated the regulation on the expression and secretion of related inflammatory factors in mice with colitis,and its impact on intestinal microbial environment.The results showed that comparing lutein crystal and its nanoparticle,lutein hydrogel alleviated dextran sodium sulfate(DSS)-induced colitis in mice more effectively by adjusting fecal heme content,colon tissue damage,and inflammatory factor levels.Moreover,lutein hydrogel increased the expression of intestinal tight junction proteins zonula occluden-1(ZO-1),claudin-1 and occludin to maintain the integrity of the intestinal-barrier,inhibited the nuclear factor-κB(NF-κB)pathway and reduced expression and secretion of inflammatory factors including tumour necrosis factor-α(TNF-α),inducible nitric oxide synthase(iNOS),NOD-like receptors 3(NLRP3)and interleukin(IL)-1β.In addition,the intestinal microbial environment of mice with colitis was improved by down-regulating the relative abundance of Desulfovibrionaceae and up-regulating the relative abundance of Erysipelotrichaceae and Rikenellaceae.As a slow-release carrier to load lutein nanoparticles,sodium alginate-based hydrogel has potential application prospect.

A STIR nucleic acid drug delivery system for stirring phenotypic switch of microglia in Parkinson’s disease treatments

Neuroinflammation is one of the three important pathological features in neurodegenerative diseases including Parkinson’s disease(PD).The regulation of neuroinflammation can reduce the severity of neurological damage to alleviate diseases.Numerous studies have shown that the phenotype switch of microglia is tightly associated with the nuclear factorκB(NF-κB)-mediated inflammatory pathway.Therefore,the small interfering RNA(siRNA)therapy for downregulating the expression of NF-κB,provides a promising therapeutic strategy for Parkinson’s disease treatments.Considering the brain delivery challenges of siRNA,a sequential targeting inflammation regulation(STIR)delivery system based on poly(amino acid)s is developed to improve the therapeutic effects of Parkinson’s disease treatments.The STIR system sequentially targets the blood–brain barrier and the microglia to enhance the effective concentration of siRNA in the targeted microglia.The results demonstrate that the STIR nanoparticles can transform microglial phenotypes and regulate brain inflammation,thus achieving neuronal recovery and abnormal aggregation ofα-synuclein protein(α-syn)reduction in the treatment of Parkinson’s disease.Herein,this STIR delivery system provides a promising therapeutic platform in PD treatments and has great potential for other neurodegenerative diseases’therapies.

Panax notoginseng Saponins Protect Kidney from Diabetes by Up-regulating Silent Information Regulator 1 and Activating Antioxidant Proteins in Rats

Objective： To explore the mechanism of the protective effects of Panax notoginseng saponins（PNS） on kidney in diabetic rats. Methods： Diabetic rat model was obtained by intravenous injection of alloxan, and the rats were divided into model, PNS-100 mg/（kg·day） and PNS-200 mg/（kg·day） groups, 10 each. Another 10 rats injected with saline were served as control. Periodic acid-Schiff staining and immunological histological chemistry were used to observe histomorphology and tissue expression of bone morphogenetic protein-7（BMP-7）. Silent information regulator 1（SIRT1） was silenced in rat mesangial cells by RNA interference. The mR NA expressions of SIRT-1, monocyte chemoattractant protein-1（MCP-1）, transforming growth factor β1（TGF-β1） and plasminogen activator inhibitor-1（PAI-1） were analyzed by reverse transcription polymerase chain reaction. The protein expressions of SIRT1 and the acetylation of nuclear factor κB（NF-κB） P65 were determined by western blotting. The concentration of MCP-1, TGF-β1 and malondialdehyde（MDA） in culture supernatant were detected by enzyme-linked immuno sorbent assay. The activity of superoxide dismutase（SOD） was detected by the classical method of nitrogen and blue four. Results： In diabetic model rats, PNS could not only reduce blood glucose and lipid（P〈0.01）, but also increase protein level of BMP-7 and inhibit PAI-1 expression for suppressing fibrosis of the kidney. In rat mesangial cells, PNS could up-regulate the expression of SIRT1（P〈0.01） and in turn suppress the transcription of TGF-β1（P〈0.05） and MCP-1（P〈0.05）. PNS could also reverse the increased acetylation of NF-κB p65 by high glucose. In addition, redox regulation factor MDA was down-regulated（P〈0.05） and SOD was up-regulated（P〈0.01）, which were both induced by SIRT1 up-regulation. Conclusions： PNS could protect kidney from diabetes with the possible mechanism of up-regulating SIRT1, therefore inhibiting inflammation through decreasing the induction of inflammatory cytokines and TGF-β1, as well as activating antioxidant proteins.