Exploring the chondroitin sulfate nanogel's potential in combating nephrotoxicity induced by cisplatin and doxorubicin-An in-vivo study on rats.

In this study, we aim to unveil the potential of itaconyl chondroitin sulfate nanogel (ICSNG) in tackling chronic kidney diseases triggered by the administration of CDDP and doxorubicin (Adriamycin, ADR). To that end, the new drug delivery system (ICSNG) was initially prepared, characterized, and loaded with the target drugs. Thereafter, the in-vivo studies were performed using five equally divided groups of 100 male Sprague-Dawley (SD) rats. Biochemical evaluation and immunohistochemistry studies have revealed the renal toxicity and the ameliorative effects of ICSNG on renal function. When ICSNG-based treatments were contrasted with the CDDP and ADR infected groups, they significantly increased paraoxonase-1 (PON-1), superoxide dismutase (SOD), catalase (CAT) and albumin activity and significantly decreased nitric oxide (NO), tumor necrosis factor alpha (TNF-α), creatinine, urea, and cyclooxygenase-2 (COX-2) activity (p < 0.001). The findings of the current study imply that ICSNG may be able to lessen renal inflammation and damage in chronic kidney disorders brought on by the administration of CDDP and ADR. Interestingly, according to the estimated selectivity indices, the ICSNG-encapsulated drugs have demonstrated superior selectivity for cancer MCF-7 cells, over healthy HSF cells, in comparison to the bare drugs.

Chemotherapeutic Activity of Imidazolium-Supported Pd(II) o-Vanillylidene Diaminocyclohexane Complexes Immobilized in Nanolipid as Inhibitors for HER2/neu and FGFR2/FGF2 Axis Overexpression in Breast Cancer Cells.

Two bis-(imidazolium-vanillylidene)-(R,R)-diaminocyclohexane ligands (H2(VAN)2dach, H2L1,2) and their Pd(II) complexes (PdL1 and PdL2) were successfully synthesized and structurally characterized using microanalytical and spectral methods. Subsequently, to target the development of new effective and safe anti-breast cancer chemotherapeutic agents, these complexes were encapsulated by lipid nanoparticles (LNPs) to formulate (PdL1LNP and PdL2LNP), which are physicochemically and morphologically characterized. PdL1LNP and PdL2LNP significantly cause DNA fragmentation in MCF-7 cells, while trastuzumab has a 10% damaging activity. Additionally, the encapsulated Pd1,2LNPs complexes activated the apoptotic mechanisms through the upregulated P53 with p < 0.001 and p < 0.05, respectively. The apoptotic activity may be triggered through the activity mechanism of the Pd1,2LNPs in the inhibitory actions against the FGFR2/FGF2 axis on the gene level with p < 0.001 and the Her2/neu with p < 0.05 and p < 0.01. All these aspects have triggered the activity of the PdL1LNP and PdL2LNP to downregulate TGFß1 by p < 0.01 for both complexes. In conclusion, LNP-encapsulated Pd(II) complexes can be employed as anti-cancer drugs with additional benefits in regulating the signal mechanisms of the apoptotic mechanisms among breast cancer cells with chemotherapeutic-safe actions.