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.

Isolation and characterization of bioactive lactoferrin from camel milk by novel pH-dependent method for large scale production.

The present article exemplifies a novel method to isolate highly purified bioactive lactoferrin from camel milk. Cytotoxicity of lactoferrin against the Hela cells was used to evaluate its bioactivity. SDS-PAGE and LC-MS analysis was done for its identification and characterization. The purified camel milk lactoferrin was found to be 708 amino acids in length with a molecular weight of 77.3 kDa and a pI value of 8.24. This pH-dependent isolation procedure ensures the retention of bioactive lactoferrin from camel milk. The importance of the present work lies in its simplicity and scalability for manufacturing bioactive lactoferrin at an industrial level.