Evaluation of the cytotoxic activity of sorafenib-loaded camel milk casein nanoparticles against hepatocarcinoma cells.

Sorafenib, a multikinase inhibitor is used to treat hepatocellular and renal carcinoma. However, a low solubility impedes its bioavailability and thus, effectiveness. This study aims to enhance its effectiveness by using novel camel milk casein nanoparticles as a delivery system. This study evaluates the cytotoxicity of sorafenib encapsulated in camel milk casein nanoparticles against human hepatocarcinoma cells (HepG2 cells) in vitro. Optimal drug loaded nanoparticles were stable for 1 month, had encapsulation efficiency of 96%, exhibited a particle size of 230 nm, zeta potential of -14.4 and poly disparity index of 0.261. Treatment with it led to cell morphology and DNA fragmentation as a characteristic of apoptosis. Flow cytometry showed G1 phase arrest of cell cycle and 26% increased apoptotic cells population upon treatment as compared to control. Sorafenib-loaded casein nanoparticles showed 6-fold increased ROS production in HepG2 cells as compared to 4-fold increase shown by the free drug. Gene and protein expression studies done by qPCR and western blotting depicted upregulation of tumor suppressor gene p53, pro-apoptotic Bax, and caspase-3 along with downregulated anti-apoptotic Bcl-2 gene and protein expression which further emphasized death by apoptosis. It is concluded regarding the feasibility of these casein nanoparticles as a delivery system with enhanced therapeutic outcomes against hepatocellular carcinoma cells.

Nothing Great Comes Without Its Risks: A Rare Case of Pembrolizumab-Induced Hypophysitis.

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein 1 and enhances immune activity against cancer cells. This has emerged as a powerful tool in the treatment of cancer in patients with severe metastatic disease. Despite this, immune checkpoint inhibitors are associated with many immune-related adverse effects. Reported endocrinopathies include thyroid dysfunction, insulin-deficient diabetes mellitus, primary adrenal insufficiency, and hypophysitis. Hypophysitis is more commonly associated with cytotoxic T-lymphocyte associated antigen 4 inhibitors like ipilimumab and rarely with pembrolizumab. A high clinical suspicion is needed to pursue a diagnosis of immune checkpoint inhibitorinduced hypophysitis, and prompt diagnosis is of immense importance due to the potentially life-threatening nature of endocrinopathies. We present a case of a 64-year-old Caucasian male individual undergoing treatment with pembrolizumab for undifferentiated lung carcinoma who subsequently developed hypophysitis.