Question

Critical thinking - Considering that chloroquine is an alkaline that targets endosomal and lysosomal pH to decrease its function (to target against virus,) how would it be delivered inside the body? Does it have to be delivered in something like a liposome since it deals with the endosome or is it just crossing the cell membrane electrostatically? Please type answer and be clear/direct.

Answer 1

1. Chloroquine functions as an effective autophagy inhibitor, by increase in lysosomal pH. This pH elevation inhibits the final steps in the autophagy pathway, leading to buildup of autophagic vesicles in the cytoplasm, which prevents the production and recycling of nutrients and metabolites and leads to cell damage and ultimately cell death . So, exposure of cancer cells to chloroquine can lead to inhibition of tumor growth and apoptosis. Tumor types that have a V600E mutation in v-Raf murine sarcoma viral oncogene homolog B (BRAF) use this as a metabolic advantage. So chloroquine can be delivered along with drugs like vemurafenib, cisplatin, or vinblastin to show greater sensitivity.

2.  Various types of drug delivery vehicles, ranging from nanosized liposomes to discoidal silicon microparticles are used to administer choroquine. Chloroquine decreases both soft (liposomes) and hard (silicon) nanomaterial deposition in the liver shows improving nanodelivery of both lipid-based nanoparticles can be successful in clinical use. Chloroquine reduces the uptake of nanoparticles by Kupffer cells, inhibits survival-promoting autophagy, and normalizes tumor vasculature for improved drug delivery.