Evaluation of F3S4-m loaded liposomes as anti-AChE and its cytotoxic activity in PC12 and HMC3 cells

Abstract

AbstractThe current research discusses the loaded of F3S4-m compound reported with multitarget activity acting as an inhibitor of acetylcholinesterase (AChE), beta-secretase 1 (BACE1), and amyloid beta (Aβ) aggregation. Despite great effort has been done to have a compound to treat Alzheimer’s disease (AD) and not only its symptomatology, nowadays there is not an effective compound in the market yet. Several synthetized compounds reported having a good activity in vitro study turned out not having it in vivo, it is believed that many of them are not able to reach the brain due to low biodisponibility, besides many of them have charged chemicals groups or tertiary amines, which have been substrates of deaminases enzymes. Therefore, the use of liposomes results an interesting strategy to deliver this kind of compounds to the brain. Then in this work it is proposed the use flexible liposomes made from phosphatidylcholine (PC) and cholesterol (Chol) to encapsulate the F3S4-m compound and evaluate its inhibitory activity against AChE. The results showed that empty liposomes particle size is influenced by the content of cholesterol in their membranes being larger for those containing 20% of cholesterol than those with 10%. The toxicity of F3S4-m loaded liposomes in PC12 cells was also evaluated employing the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay (MTT). The results showed that F3S4-m loaded liposomes can inhibit the enzymatic activity of AChE, but the concentration of encapsulated F3S4-m needed to inhibit AChE was 2-times higher than what was previously reported in solution. Graphical abstract