Preclinical and Clinical Studies

Abstract

Contemporary drug pipelines are increasingly populated with difficult‐to‐formulate drug substances. Amorphous solid dispersions can increase drug dissolution rate by reducing the effective drug particle size through its dispersion in the matrix. Based on the theorized way of working of amorphous solid dispersions, one of the most important design elements is their ability to dissolve and supersaturate. This is initially assessed in vitro through the use of dissolution protocols especially set up for that purpose. A number of in vivo assessments of the potential utility of amorphous solid dispersions have been completed using various animal models. Clinical assessments to investigate itraconazole supersaturation (indirectly) have also been completed. Itraconazole is a widely studied compound in this context with numerous in vitro , in vivo , and clinical evaluations completed. Useful preclinical and clinical models for assessing solid dispersion fitness will contribute to the drug development process.

Shrimp miR-965 induced the human melanoma stem-like cell apoptosis and inhibited their stemness by disrupting the MCL-1-ER stress-XBP1 feedback loop in a cross-species manner

“…Featured with metabolic adaptation, CSCs are considered to possess slower cycling rate than differentiated cancer cells; they are able to re-enter into the cell cycle after radiotherapy or chemotherapy, while most differentiated cancer cells die or undergo cell cycle arrest [7,8]. Strategies targeting cancer stem cells have been explored including intervention of signaling pathways involved in CSC self-renew or self-maintenance [9]. Myeloid cell leukemia sequence 1(MCL-1) is an anti-apoptotic protein, which belongs to BCL-2 protein family and is primarily located in the mitochondria, in which it inserts into the mitochondrial membrane via a hydrophobic tail and is implicated in the ER-mitochondria signaling transmission [10][11][12].…”