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Hesperidin (Hes) protects different organs from damage by acting as a potent antioxidant and anti-inflammatory. This study aims to evaluate the gastroprotective effects of free hesperidin and its chitosan nanoparticles (HNPs) against ethanol-induced gastric ulcers in rats, hypothesizing that HNPs will enhance bioavailability and therapeutic efficacy due to improved solubility and targeted delivery. HNPs were synthesized via ion gelation and characterized using TEM, SEM, and zeta potential analyses. Key assessments included gastric acidity, histological analysis, and markers of inflammation, oxidative stress, and apoptosis. HNPs significantly decreased gastric acidity, reduced inflammatory and apoptotic markers, and enhanced antioxidant enzyme activities compared to free hesperidin and esomeprazole. Furthermore, Sirt-1, PGC-1α, HO-1, and FOXO1 gene expression were also evaluated. HNPs raised Sirt-1, PGC-1α, HO-1, and downregulated FOXO1, and they suppressed the activities of NF-κB p65, COX-2, IL-1β, CD86, FOXO1 P53, and caspase-3 and increased Sirt-1 activity. HNPs treatment notably restored antioxidant enzyme activity, reduced oxidative stress and inflammatory markers, and improved histological outcomes more effectively than free hesperidin and esomeprazole. These results indicate that chitosan nanoparticles significantly enhance the gastroprotective effects of hesperidin against ethanol-induced gastric ulcers, potentially offering a more effective therapeutic strategy. Further research should explore the clinical applications of HNPs in human subjects.

Musculoskeletal pain and inflammation can vary from localised pain like pain in the shoulders and neck to widespread pain like fibromyalgia, and as per estimates, around 90% of humans have experienced such pain. Oral non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for such conditions but are associated with concerns like gastric irritation and bleeding. In the present study, a microemulsion-based gel comprising β-caryophyllene, isopropyl myristate, Tween 80, and normal saline was prepared as a topical option for managing topical pain and inflammation. The globules of the microemulsion were below 100 nm with a zetapotential of around −10 mV. The drug entrapment was >87% with a drug loading of >23%. The permeation studies established better skin permeation (20.11 ± 0.96 μg cm−2 h−1) and retention of the drug (4.96 ± 0.02%) from the developed system vis-à-vis the conventional product (9.73 ± 0.35 μg cm−2 h−1; 1.03 ± 0.01%). The dermatokinetic studies established the better pharmacokinetic profile of the bioactive in the epidermis and dermis layers of the skin. The anti-inflammatory potential in carrageenan-induced rat paw oedema was more pronounced than the conventional product (~91% vis-à-vis ~77%), indicating a better pharmacodynamic outcome from the developed system. The nanotechnology-based natural bioactive product with improved efficacy and drug loading can provide a better alternative for the management of musculoskeletal pain.

In the 21st century, melanoma and non-melanoma skin cancers have become an epidemic outbreak worldwide. Therefore, the exploration of all potential preventative and therapeutic measures based on either physical or bio-chemical mechanisms is essential via understanding precise pathophysiological pathways (Mitogen-activated protein kinase, Phosphatidylinositol 3-kinase Pathway, and Notch signaling pathway) and other aspects of such skin malignancies. Nano-gel, a three-dimensional polymeric cross-linked porous hydrogel having a diameter of 20–200 nm, possesses dual properties of both hydrogel and nanoparticle. The capacity of high drug entrapment efficiency with greater thermodynamic stability, remarkable solubilization potential, and swelling behavior of nano-gel becomes a promising candidate as a targeted drug delivery system in the treatment of skin cancer. Nano-gel can be either synthetically or architectonically modified for responding to either internal or external stimuli, including radiation, ultrasound, enzyme, magnetic, pH, temperature, and oxidation-reduction to achieve controlled release of pharmaceuticals and several bio-active molecules such as proteins, peptides, genes via amplifying drug aggregation in the active targeted tissue and reducing adverse pharmacological effects. Several drugs, such as anti-neoplastic biomolecules having short biological half-lives and prompt enzyme degradability capacity, must be appropriate for administration employing either chemically bridged or physically constructed nano-gel frameworks. The comprehensive review summarizes the advancement in the preparation and characterization methods of targeted nano-gel with enhanced pharmacological potential and preserved intracellular safety limits for the mitigation of skin malignancies with a special emphasize on skin cancer inducing pathophysiological pathways and prospective research opportunities for skin malignancy targeted nano-gels.

Sortase A (SrtA) is an enzyme which attaches proteins, including virulence factors, to bacterial cell walls. It is a potential target for developing anti-virulence agents against pathogenic and antimicrobial resistant bacteria. This study aimed to engineer 𝛽-lactoglobulin protein nanoparticles (PNPs) for encapsulating safe and inexpensive natural SrtA inhibitors (SrtAIs; trans-chalcone (TC), curcumin (CUR), quercetin (QC), and berberine (BR)) to improve their poor aqueous dispersibility, to screen for synergy with antimicrobial peptides (AMPs), and to reduce the cost, dose, and toxicity of AMPs. Minimum inhibitory concentration (MIC), checkerboard synergy, and cell viability assays were performed for SrtAI PNPs against Gram-positive (methicillin-sensitive and -resistant S. aureus) and Gram-negative (E. coli, P. aeruginosa) bacteria alone and combined with leading AMPs (pexiganan, indolicidin, and a mastoparan derivative). Each SrtAI PNP inhibited Gram-positive (MIC: 62.5–125 µg/mL) and Gram-negative (MIC: 31.3–500 µg/mL) bacterial growth. TC PNPs with pexiganan demonstrated synergy against each bacteria, while BR PNPs with pexiganan or indolicidin provided synergy towards S. aureus. Each SrtAI PNP inhibited SrtA (IC50: 25.0–81.8 µg/mL), and did not affect HEK-293 cell viability at their MIC or optimal synergistic concentrations with AMPs. Overall, this study provides a safe nanoplatform for enhancing antimicrobial synergy to develop treatments for superbug infections.

This study aimed to develop synergistic therapies to treat superbug infections through the encapsulation of sortase A inhibitors (SrtAIs; trans-chalcone (TC), curcumin (CUR), quercetin (QC), or berberine chloride (BR)) into MCM-41 mesoporous silica nanoparticles (MSNs) or a phosphonate-modified analogue (MCM-41-PO3−) to overcome their poor aqueous solubility. A resazurin-modified minimum inhibitory concentration (MIC) and checkerboard assays, to measure SrtAI synergy in combination with leading antimicrobial peptides (AMPs; pexiganan (PEX), indolicidin (INDO), and [I5, R8] mastoparan (MASTO)), were determined against methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The results demonstrated that the MCM-41 and MCM-41-PO3− formulations significantly improved the aqueous solubility of each SrtAI. The MICs for SrtAI/MCM-41-PO3− formulations were lower compared to the SrtAI/MCM-41 formulations against tested bacterial strains, except for the cases of BR/MCM-41 and QC/MCM-41 against P. aeruginosa. Furthermore, the following combinations demonstrated synergy: PEX with TC/MCM-41 (against all strains) or TC/MCM-41-PO3− (against all strains except P. aeruginosa); PEX with BR/MCM-41 or BR/MCM-41-PO3− (against MSSA and MRSA); INDO with QC/MCM-41 or QC/MCM-41-PO3− (against MRSA); and MASTO with CUR/MCM-41 (against E. coli). These combinations also reduced each components’ toxicity against human embryonic kidney cells. In conclusion, MCM-41 MSNs provide a platform to enhance SrtAI solubility and demonstrated antimicrobial synergy with AMPs and reduced toxicity, providing novel superbug treatment opportunities.