Background and Objectives: Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer many valuable opportunities in drug delivery. Chlorpromazine, an antipsychotic agent with poor aqueous solubility—with extensive first-pass metabolism—can be a suitable candidate for the development of SNEDDS. The current study was designed to develop triglyceride-based SNEDDS of chlorpromazine to achieve improved solubility, stability, and oral bioavailability. Materials and Methods: Fifteen SNEDDS formulations of each short, medium, and long chain, triglycerides were synthesized and characterized to achieve optimized formulation. The optimized formulation was characterized for several in vitro and in vivo parameters. Results: Particle size, zeta potential, and drug loading of the optimized SNEDDS (LCT₁₄) were found to be 178 ± 16, −21.4, and 85.5%, respectively. Long chain triglyceride (LCT₁₄) showed a 1.5-fold increased elimination half-life (p < 0.01), up to 6-fold increased oral bioavailability, and 1.7-fold decreased plasma clearance rate (p < 0.01) compared to a drug suspension. Conclusion: The findings suggest that SNEDDS based on long-chain triglycerides (LCT₁₄) formulations seem to be a promising alternative for improving the oral bioavailability of chlorpromazine.

Background: New approaches for the prevention of colon cancer perseveres an essential necessity. Though, resistance to existing chemo-preventive drugs is moderately predominant in colon carcinogenesis. Taxifolin (dihydroquercetin) is a flavononol, have shown virile biological activities against few cancers. The current study was designed to investigate and equate antitumor activity of Taxifolin (TAX) in colorectal cancer cell lines and in HCT116 xenograft model in a comprehensive approach. Methods: Two human colorectal cancer cell lines HCT116 and HT29, were used. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide (MMT) protocol was performed to elucidate the impact of TAX and β- catenin inhibitor (FH535) on the viability of HCT116 and HT29 cell lines. Apoptosis /cell cycle assay was performed. Data interpretation was done with a FACScan (Becton Dickinson, NJ). About 1 × 10 ⁴ cells per sample were harvested. Histograms of DNA were analyzed with ModiFitLT software (verity Software House, ME, USA). Western blotting and RT-PCR were performed for protein and gene expression respectively in in vitro and in vivo . Results: We found that TAX induced cytotoxicity in colorectal cells in a dose-dependent manner and time dependent approach. Further, our data validated that administration of TAX to human colorectal cancer HCT116 and HT29 cells resulted in cell growth arrest, variation in molecules controlling cell cycle operative in the G2 phase of the cell cycle and apoptosis in a concentration dependent approach. Further our results concluded that TAX administration decreases expression of β-catenin gene , AKT gene and Survivin gene and protein expression in in vitro and in vivo . Conclusion: Our findings proposed that targeting β-catenin gene may encourage the alterations of cell cycle and cell cycle regulators. Wnt/ β-catenin signaling pathway possibly takes part in the genesis and progression of colorectal cancer cells through regulating cell cycle and the expression of cell cycle regulators.

Background: More than the two decades, the question of whether vitamin D has a role in cancer frequency, development, and death has been premeditated in detail. Colorectal, breast, and prostate cancers have been a scrupulous spot of center, altogether, these three malignancies report for approximately 35% of cancer cases and 20% of cancer demises in the United States, and as such are a chief public health apprehension. The aim was to evaluate antitumor activity of Vitamin D-Nanoemulsion (NVD) in colorectal cancer cell lines and HCT116 xenograft model in a comprehensive approach. Methods: Two human colorectal cancer cell lines HCT116 and HT29 (gained from College of Pharmacy, King Saud University, KSA were grown. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide protocol were performed to show the impact of NVD and β-catenin inhibitor (FH535) on the viability of HCT116 and HT29 cell lines. Apoptosis/cell cycle assay was performed. Analysis was done with a FACScan (Becton–Dickinson, NJ). About 10,000 cells per sample were harvested and Histograms of DNA were analyzed with ModiFitLT software (verity Software House, ME, USA). Western blotting and RT-PCR were performed for protein and gene expression respectively in in vitro and in vivo. Results: We found that NVD induced cytotoxicity in colorectal cells in a dose-dependent manner and time dependent approach. Further, our data validated that NVD administration of human colorectal cancer HCT116 and HT29 cells resulted in cell growth arrest, alteration in molecules regulating cell cycle operative in the G2 phase of the cell cycle and apoptosis in a dose dependent approach. Further our results concluded that NVD administration decreases expression of β-catenin gene, AKT gene and Survivin gene and protein expression in in vitro and in vivo. Conclusion: Our findings suggest that targeting β-catenin gene may encourage the alterations of cell cycle and cell cycle regulators. Wnt/β-catenin signaling pathway possibly takes part in the genesis and progression of colorectal cancer cells through regulating cell cycle and the expression of cell cycle regulators.

Bisphenol S has been introduced into some industrial applications and it may act as a xeno-estrogen that can alter endocrine functions and reproduction. The present study was carried out to examine the effect of bisphenol S exposure on oxidative stress, generation of reactive oxygen species, and DNA integrity in rat spermatozoa in vitro and daily sperm production and sperm DNA damage in vivo. Sperm were incubated with bisphenol S at concentrations of 0.5, 1, 10, and 100 µg/L. At the highest concentration, bisphenol S induced formation of reactive oxygen species, caused lipid peroxidation, affected superoxide dismutase levels, and increased DNA fragmentation. Adult rats were exposed to doses of 0.5, 5, 25, and 50 µg/kg/d for 28 days. Decrease in daily sperm production and an increase in sperm DNA damage was observed at the highest dose in the 50 µg/kg/d treated group, but sperm motility was not reduced.

The current research focused on the chronic effect of arsenic (As³⁺, As III) on the reproductive system in male rats. Fifty male rats (190 ± 10 g) were separated into five groups to assess Arsenic induced physiological, hormonal and histopathological impairments. Following the dissection, blood, vital organs, accessory reproductive, testicular and hypothalamic tissues were obtained. Blood plasma was isolated and preserved for determining oxidative stress and performing hormonal analysis, while epididymis was used for sperm parameters assessment, and testis were subjected to histological analysis. The results revealed a significant decrease in percent sperm motility, sperm viability, and daily sperm production rate in high-dose treatment groups (25 and 50 mg/L). The concentrations of catalase, superoxide dismutase, and peroxidase were found to be significantly reduced. At the same time, a remarkable increase in reactive oxygen species (ROS) and thiobarbituric acid reactive species (TBARs) and was evident in a dose-dependent manner. Similarly, significantly low amounts of plasma testosterone, follicle-stimulating hormones (FSH), and luteinizing hormone (LH) were noted among treatment groups after exposure to arsenic. Histopathological findings showed remarkable multiple degenerations in seminiferous tubules including tubular atrophy, Leydig cells hypoplasia, proliferative marginal neoplasia, severe necrosis and acute germ cell aplasia leading to Sertoli cell-only syndrome. Fluorescent immune-cyto-chemical data confirmed a dose-proportional lowered quantitative expression in the number of gonadotrophins releasing hormone (GnRH) like immunoreactive (IR) neurons. Analysis of the comet assay revealed intensified nuclear denaturation and sperm DNA fragmentation in As³⁺ treated groups vs. the control. "Arsenic exposure induces oxidative stress, disrupts hormonal balance, impairs spermatogenesis, and causes testicular damage and DNA fragmentation, ultimately leading to reduced male fertility."