Methotrexate (MTX), the gold standard against psoriasis, poses severe problems when administered systemically viz increased toxicity, poor solubility and adverse reactions. Hence, a topical formulation of MTX for the management of psoriasis can be an effective approach. The present study aimed to develop an MTX based nanoparticle-loaded chitosan hydrogel for evaluating its potential efficacy in an imiquimod-induced psoriatic mice model. MTX-NPs loaded hydrogel was prepared and optimized using the o/w emulsion solvent evaporation method. Particle size, zeta potential, entrapment efficiency, in vitro drug release, ex vivo permeation, skin irritation and deposition studies were performed. Psoriatic Area and Severity Index (PASI) score/histopathological examinations were conducted to check the antipsoriatic potential of MTX-NPs loaded hydrogel using an imiquimod (IMQ)-induced psoriatic model. Optimized MTX-NPs showed a particle size of 256.4 ± 2.17 nm and encapsulation efficiency of 86 ± 0.03%. MTX-NPs loaded hydrogel displayed a 73 ± 1.21% sustained drug release in 48 h. Ex vivo permeation study showed only 19.95 ± 1.04 µg/cm² of drug permeated though skin in 24 h, while epidermis retained 81.33% of the drug. A significant decrease in PASI score with improvement to normalcy of mice skin was observed. The developed MTX-NPs hydrogel displayed negligible signs of mild hyperkeratosis and parakeratosis, while histopathological studies showed healing signs of mice skin. So, the MTX-NPs loaded hydrogel can be a promising delivery system against psoriasis.

Chronic wound infections have become a challenging problem due to escalating antibiotic resistance and lack of viable delivery approaches. Carvacrol (CAR) has been reported to be effective against multidrug resistant pathogens. In this study, CAR was formulated into a site-specific nanoparticle (NP) delivery system using poly(caprolactone) (PCL) to achieve a sustained antimicrobial effect at infection sites. These NPs were further incorporated into dissolving microneedles (MNs) to facilitate painless application and overcome the necrotic tissue barrier which hinders drug penetration into wound bed. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacteria, highlighting its potential for on-demand delivery. Moreover, encapsulation of CAR in PCL NPs resulted in 2-4 fold increase in its antimicrobial activity. Dermatokinetic studies revealed that CAR-PCL NPs-MNs were able to enhance skin retention of CAR after 24 h (83.8 ± 5.15%), compared to free CAR-MNs (7.3 ± 2.04%). Importantly, this novel approach exhibited effective antimicrobial activity in an ex-vivo wound model. Hence, these findings have proven the concept that loading of CAR into this advanced MNs platform can lead to sustained antimicrobial effect at desired site and may provide a novel effective approach for treatment of infected wounds. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.

Background: In the present study, the poncirin which is flavonoid-7-o-glycosides (isolated from the Poncirus trifoliata) in nature was evaluated against the Carbon tetra chloride (CCL4)-induced liver injury. The poncirin have been reported for various anti-inflammatory, analgesic activity etc. Based on the previous studies it was anticipated that the poncirin will ameliorate CCL4-induced liver injury. Methods: The CCL4-induced acute and chronic liver injury model (albino BALB/c mice) was used. Following the induction of the liver injury various parameters such as food and water intake, body weight and weight to dry ratio changes were assessed. Furthermore, various hematological, biochemical parameters and histological studies such as hemotoxylin and eosin (H and E) staining were performed. The poncirin treatment was also evaluated against the pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) using enzyme link immunosorbant assay (ELISA). The Swiss Target prediction software was used to investigate interaction of the poncirin on the various hepatic enzymes. Results: The poncirin treatment markedly improved the behavioral parameters such as food and water intake. The liver weight variation was attenuated and total body was improved markedly. The hematological and biochemical parameters were significantly improved compared to the CCL4 treated groups. The anti-oxidants were induced, while oxidative stress markers were reduced promisingly. The H and E staining showed that poncirin treatment significantly improved the histology of liver compared to the CCL4 treated group. Furthermore, the poncirin treatment also evidently decreased the inflammatory mediators. Conclusions: The poncirin treatment showed marked improvement in behavioral, biochemical and histological parameters following CCL4-induced liver injury. Additionally, the poncirin treatment also markedly improved the antioxidant enzymes, attenuated the oxidative stress markers and inflammatory cytokines.