pH-Sensitive nanoparticles containing 5-fluorouracil and leucovorin as an improved anti-cancer option for colon cancer

Parenteral administration of chemotherapeutic drugs, 5-fluorouracil (5-FU) and leucovorin (LV), is commonly used to treat large bowel carcinomas such as colon cancer (CC) and colorectal carcinoma (CRC). Our study aims to design a novel nanoparticulate drug-delivery vehicle for oral use capable of colon-specific release. A modified double-emulsion solvent evaporation method was used in the preparation of pH-responsive Eudargit S100 polymeric nanoparticles, loaded with 5-FU/LV combination (5-FU/LV-loaded Eudargit S100 NPs). Our optimized drug-loaded NP showed a pH-responsive drug release and exhibited significantly more cytotoxic actions in cancer-cell lines than free drugs. These findings open the way for conducting clinical trials for colon malignancies treated with nanoparticles

Efficacy of resveratrol encapsulated microsponges delivered by pectin based matrix tablets in rats with acetic acid-induced ulcerative colitis

Objectives: The objective of the present work to encapsulate the resveratrol (RES) inside the chitosan-based microsponges, employing the systematic optimization by 33 Box-Behnken design for the colonic targeting.Significance: Enhanced therapeutic efficacy of RES-loaded microsponges and matrix tablets, vis-a-vis pureRES for ulcerative colitis.Methods: RES-loaded microsponges were prepared employing the systematic optimization by 33 Box-Behnken design for the colonic targeting. The best-optimizedRES-loaded microsponge was compressed in the form of a tablet, employing pectin as a matrix-forming material. The encapsulation of RES inside microsponge was confirmed by XRD, DSC and FT-IR. Further, both RES-loaded microsponges and matrix tablets were evaluated for in vitro release kinetics and further evaluated for in vivo ulcerative colitis animal model.Results: Optimization experiments was obtained as the high value of r2 (particle size = 0.9999; %EE = 0.9652; %CDR = 0.9469) inferred excellent goodness of fit. SEM revealed nearly spherical and porous nature of RES-loaded microsponges. The in vitro release kinetic showed zero-order release for RES-loaded microsponges and Korsmeyer-Peppas model for matrix tablets. The pharmacodynamic studies, in ulcerative colitis rat model, indicated better therapeutic efficacy of drug-loaded microsponges and matrix tablets, vis-a-vis pure RES. Thus, the present study advocates the potential of RES based microsponges delivered by pectin based matrix tablet, in the treatment of various colonic disorders.Conclusion: The present study proved that RES-loaded microsponges and matrix tablets based on chitosan and pectin can be the ideal delivery system for colonic delivery of RES

Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Hypoglycemia

A relatively recent addition to the arsenal of antidiabetic drugs used for the treatment of type 2 diabetes mellitus (T2DM) has been the “incretin mimetics,” a group of drugs that work on the glucagon-like peptide-1 (GLP-1) receptor and enhance insulin secretion from the pancreatic β-cells in a glucose-dependent manner, more potently in hyperglycemic conditions, while suppressing glucagon secretion at the same time. Therefore, it was assumed that this class of drugs would have a lower risk of hypoglycemia than insulin secretagogues like sulphonylureas. However, GLP-1 receptor agonists have been proposed to cause hypoglycemia in healthy normoglycemic subjects implying that their action is not as glucose-dependent as once thought. Other studies concluded that they might not induce hypoglycemia and the risk is dependent on other individual factors. However, the FDA announced that the 12 GLP-1 receptor agonists currently available on the market had potential safety signs and evaluated the need for regulatory action. This review provides an overview of the studies that investigated the possible hypoglycemic effect of GLP-1 receptor agonists. In addition, the current review describes other adverse effects of GLP-1 receptor agonist treatment

SARS‐CoV‐2 research using human pluripotent stem cells and organoids

Experimental cell models are indispensable for clarifying the pathophysiology of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and for developing therapeutic agents. To recapitulate the symptoms and drug response of COVID-19 patients in vitro, SARS-CoV-2 studies using physiologically relevant human embryonic stem (ES)/induced pluripotent stem (iPS) cell-derived somatic cells and organoids are ongoing. These cells and organoids have been used to show that SARS-CoV-2 can infect and damage various organs including the lung, heart, brain, intestinal tract, kidney, and pancreas. They are also being used to develop COVID-19 therapeutic agents, including evaluation of their antiviral efficacy and safety. The relationship between COVID-19 aggravation and human genetic backgrounds has been investigated using genetically modified ES/iPS cells and patient-derived iPS cells. This review summarizes the latest results and issues of SARS-CoV-2 research using human ES/iPS cell-derived somatic cells and organoids