Various vesicle-based therapeutic strategies have recently been investigated as potential approaches for skin rejuvenation and anti-aging. In this study, the rejuvenating effects of Citrus lemon-derived nanovesicles (CLDNVs) on photoaged skin were evaluated in a murine model. CLDNVs were isolated and characterized based on their morphology, concentration, particle size, and surface markers. The cytotoxicity of CLDNVs on human dermal fibroblast cells was assessed using the MTT assay. Female C57BL/6 mice were exposed to UVB radiation for 10 weeks to induce photoaging. Subsequently, they were treated for 28 days with CLDNVs (300 µg/mL) either alone or in combination with 0.05
Coronavirus disease 2019 (COVID-19) has highlighted the need for novel antiviral agents with additional therapeutic activities against inflammatory and opportunistic fungal infections, including mucormycosis. To evaluate the in vitro antioxidant, anti-inflammatory, antifungal, and antiviral activities of ethanolic leaf and stem bark extract of Jatropha integerrima (JIJ) and its in vivo efficacy against Human Coronavirus 229E (HCoV-229E). Antioxidant activity was assessed using DPPH and ABTS assays. Anti-inflammatory activity was evaluated in lipopolysaccharide (LPS)-stimulated THP-1 monocytes and RAW 264.7 macrophages by analysing TNF-α and iNOS gene expression. Antifungal activity was investigated against Apophysomyces elegans and Rhizopus oryzae. Cytotoxicity and antiviral activity were assessed in A549 cells. Optimized JIJ-containing self-nanoemulsifying drug delivery system (JIJ-SNEDDS) was evaluated in BALB/c mice intranasally infected with HCoV-229E. JIJ exhibited strong antioxidant activity, downregulated TNF-α and iNOS expression, and demonstrated antifungal activity against both fungal pathogens. The extract inhibited viral replication in A549 cells with minimal cytotoxicity. Optimized JIJ-SNEDDS exhibited a particle size of 115 ± 1.4 nm and zeta potential of − 32.7 ± 2.1 mV. In infected mice, treatment markedly reduced lung viral load and histopathological damage. RT-PCR and protein analyses confirmed decreased viral RNA and protein levels. Flow cytometry revealed an increased Th1/Th2 ratio, decreased Th17/Treg ratio, and increased B- and natural killer (NK)-cell populations. Serum interleukin-6 (IL-6) and TNF-α levels were also reduced. JIJ-SNEDDS demonstrated promising preclinical antiviral activity against HCoV-229E, accompanied by immunomodulatory and anti-inflammatory effects. These findings warrant further investigation of its therapeutic potential against coronavirus infection and associated inflammatory complications.
The subcutaneous (sub-Q) delivery of tofacitinib citrate (TOFA) can be a promising alternative to overcome oral associated side effects and complications . The study aimed to address HSPiP based predicted solubility and solubility behaviour of TOFA in various mass ratios (m = 0.0–1.0) of PEG400 in PEG400-water system T = 298.15–318.15 K. Hansen solubility parameters were estimated and the experimental solubility data were validated using various models (Van’t Hoff, Apelblat, Roseman-Yalkowsky, and thermodynamic models). Finally, the stability study was conducted to estimate TOFA shelf-life, followed by GastroPlus-based predictive in vivo performance in humans. PEG400 addition resulted in reduced δp and δh values up to m = 0.5, which may be correlated to the effective disruption of extensive H-bond network strength and decreased overall polarity of water by PEG400, as predicted in HSPiP. The temperature-dependent solubility was validated with the models. The binary system (m = 0.5) exhibited stable solubility, suitable for sub-Q delivery. The enthalpy-entropy compensation temperature (Tc) was 59.5 °C, suggesting constant ΔsolG° over m = 0.1–0.9 of PEG400. Thus, TOFA solubility and stability were temperature, mass, and pH dependent. GastroPlus software predicted improved pharmacokinetic parameters and extended in vivo absorption following sub-Q delivery at m = 0.5 in humans. Thus, a stable sub-Q product can be a promising alternative to the conventional tablet of TOFA.
To develop and optimize a progesterone-loaded thermosensitive in situ gel system for the sustained delivery of progesterone, aiming to enhance progesterone exposure, pharmacokinetic characteristics and patient compliance in the management of conception failures associated with progesterone deficiency. A Central Composite Design (CCD) was utilized to systematically optimize the concentrations of Poloxamer 407 and hydroxypropyl methylcellulose (HPMC). The formulation was evaluated based on critical response parameters, including gelation time and viscosity. Comprehensive characterization was performed through pH measurement, rheological assessment, and drug content uniformity analysis. Solid-state properties were investigated using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Furthermore, in vitro release kinetics were monitored for 120 h; in vivo pharmacokinetic studies were assessed by LC‒MS/MS method validation; and pharmacodynamic profiles were evaluated in bubalus bubalis compared with a GnRH-based Ov synch (GPG) protocol. The optimized developed progesterone-loaded thermosensitive in situ gel formulation exhibited reproducible thermogelling behaviour within the physiological temperature with an acceptable gelation time of approximately 56 s. Solid-state characterization suggested reduced crystallinity and possible amorphous dispersion of progesterone within the polymeric matrix with no evidence of chemical incompatibility. The system maintained uniformity of drug content (> 95
Diabetes mellitus (DM) and sleep disturbances are associated with cognitive impairment and hippocampal dysfunction, potentially involving oxidative stress and neuroinflammation. This study investigated the effects of vitamins C and E, individually and in combination, to determine whether their complementary antioxidant properties provide enhanced neuroprotective effects against cognitive and hippocampal alterations in diabetic sleep-deprived mice. Diabetes was induced in male BALB/c mice (25–30 g) by streptozotocin (60 mg/kg), followed by partial sleep deprivation using the inverted flowerpot method. Animals received vitamin C (50 mg/kg), vitamin E (100 mg/kg), or their combination for 20 days. Body weight and blood glucose were monitored. Spatial learning and memory were evaluated using the Morris water maze. Hippocampal histopathology, GFAP immunostaining, and expression of genes related to oxidative stress, inflammation, and neuroprotection were assessed. Vitamin E and combined vitamin C and E treatment reduced FBG and were associated with higher final body weight than untreated diabetic sleep-deprived mice. Vitamin treatments improved spatial learning and memory, with combined treatment producing greater improvements in selected behavioral outcomes. Combined treatment increased hippocampal neuronal density and reduced GFAP immunoreactivity. Vitamin treatment increased BDNF, Nrf2, and HO-1 expression and reduced iNOS, TNF-α, and IL-1β expression. Vitamin C and E, particularly in combination, were associated with improved metabolic, cognitive, and hippocampal outcomes in diabetic sleep-deprived mice, potentially involving modulation of neuroinflammatory and oxidative stress-related markers. Combined vitamin C and E treatment improved spatial memory deficits in diabetic sleep-deprived mice. Vitamin C and E treatment attenuated hippocampal neuronal and histopathological. alterations. Combined treatment increased hippocampal BDNF, Nrf2, and HO-1 gene expression. Vitamin C and E treatment reduced hippocampal iNOS, TNF-α, and IL-1β gene expression.
