To evaluate and compare the efficacy of rapamycin used topically in a mouse model of herpetic stromal keratitis. The corneas were infected with herpes simplex virus type-1 strain KOS. Animals were divided into: control (CG), rapamycin (RAPA), cyclosporine (CsA), and dexamethasone (DEXA). The evolution of the disease was assessed clinically and histologically. On day 10 postinfection (pi), the RAPA group showed only a significantly lower angiogenic development than the CG. On day 14 pi, the treated groups had significantly lower scores for angiogenesis and necrosis than the CG. Also, on day 14 pi, the RAPA and DEXA groups showed significantly lower histopathological scores compared to the CG. The topical application of 0.05% rapamycin showed greater efficacy than 0.5% cyclosporine and similar efficacy to 0.1% dexamethasone to minimize the immuno-inflammatory process. Also, rapamycin showed early inhibition of the formation of new vessels.

Background/Objectives: Drug repurposing explores new applications for approved medications, such as simvastatin (SV), a lipid-lowering drug that has shown anticancer potential but is limited by solubility and side effects. This study aims to enhance SV delivery and efficacy against lung cancer cells using bioactive lipid nanoparticles formulated with plant-derived monoterpenes as both nanostructuring agents and anticancer molecules. Methods: Lipid nanoparticles were produced by ultrasonication and characterized for morphology, size, zeta potential, and polydispersity index (PDI). Monoterpenes (linalool-LN-, limonene, 1,8-cineole) or Crodamol^® were used as liquid lipids. Encapsulation efficiency (EE), release profiles, stability, biocompatibility, protein adsorption, cytotoxicity, and anticancer effects were evaluated. Results: The nanoparticles exhibited high stability, size: 94.2 ± 0.9–144.0 ± 2.6 nm, PDI < 0.3, and zeta potential: −4.5 ± 0.7 to −16.3 ± 0.8 mV. Encapsulation of SV in all formulations enhanced cytotoxicity against A549 lung cancer cells, with NLC/LN/SV showing the highest activity and being chosen for further investigation. Sustained SV release over 72 h and EE > 95% was observed for NLC/LN/SV. SAXS/WAXS analysis revealed that LN altered the crystallographic structure of nanoparticles. NLC/LN/SV demonstrated excellent biocompatibility and developed a thin serum protein corona in vitro. Cellular studies showed efficient uptake by A549 cells, G0/G1 arrest, mitochondrial hyperpolarization, reactive oxygen species production, and enhanced cell death compared to free SV. NLC/LN/SV more effectively inhibited cancer cell migration than free SV. Conclusions: NLC/LN/SV represents a promising nanocarrier for SV repurposing, combining enhanced anticancer activity, biocompatibility, and sustained stability for potential lung cancer therapy.

Copper (Cu) is an essential trace metal; however, its dysregulation promotes oxidative stress and contributes to neurodegeneration. Astrocytes are central to neuronal homeostasis, in part through extracellular vesicle (EV)-mediated communication, yet they are particularly vulnerable to metal-induced oxidative damage. Under pathological conditions, astrocyte-derived EVs can acquire neurotoxic properties, thereby amplifying neuronal injury. However, the mechanisms governing neuron–glia crosstalk under Cu overload remain incompletely defined. Here, we show that sublethal Cu exposure induces mitochondrial oxidative stress in astrocytes, leading to redox-dependent reprogramming of cholesterol metabolism and alterations in EV release. EVs derived from Cu-overloaded astrocytes propagate oxidative damage to neurons, establishing a ROS-driven pathway of glia-to-neuron communication. Notably, activation of insulin-like growth factor 1 (IGF-1) signaling—via recombinant protein or adenoviral delivery—attenuates Cu-induced oxidative stress, partially restores cholesterol metabolic homeostasis, and reprograms astrocyte-derived EVs toward a non-cytotoxic phenotype. Collectively, these findings identify astrocyte-derived EVs as key mediators of Cu-induced neuronal injury and highlight IGF-1 signaling as a potential therapeutic strategy to preserve astrocyte oxidative resilience and neuroprotective function.