Study on development and tissue permeation of different formulations of Fasudil.

OBJECTIVE: The study is intended to formulate Fasudil loaded vesicular system for application in the management of angina. MATERIALS AND METHODS: Fasudil was made into a complex with phospholipid, and other different formulations were made, including Fasudil solution, liposomal form, and Fasudil loaded into the gel. A drug characterization study was conducted and noted. Drug release was quantified and analyzed and, finally, inoculated in Sprague-Dawley rats. These rats underwent anginal induction, and each formulation's effect on angina was evaluated. RESULTS: Drug solution (F-Phos) and F-Phos-Lipo (liposomal dispersion form of the drug) have shown that more than half percent of them have been released within 1.5 hours, and the rapid release occurred from liposomal dispersion in the first hour. The study determined the viscosity of the different formulations, which was significantly (p<0.05) higher than the theoretical sum of the viscosity of each formulation. The study found that the F-Phos-Lipo+P-407HMS formulation is the most effective as its application has the minimum infarct area percentage compared to the other formulations and can also reduce creatine kinase levels significantly as compared to the different formulations (p<0.05). CONCLUSIONS: The study concluded that the typical gel formulation (liposomal Fasudil dispersed in hydroxypropyl methylcellulose solution, which is added to blank poloxamer 407) had been shown to have significantly anti-anginal properties, including easy administration, its application on the infarct area percentage and subsequently its pharmacological effect on the cardiac tissue.

Beta Elemene induces cytotoxic effects in FLT3 ITD-mutated acute myeloid leukemia by modulating apoptosis.

OBJECTIVE: ß-Elemene, a sesquiterpene with a broad anti-cancer spectrum, is particularly effective against drug-resistant and complex tumors. It can also be efficient against FLT3-expressed acute myeloid leukemia. This research aims to determine whether ß-Elemene has cytotoxic effects on FLT3 ITD-mutated AML cells. MATERIALS AND METHODS: Cytotoxicity, cell morphology, mRNA analysis with apoptotic markers, and analysis of 43 distinct protein markers related to cell death, survival, and resistance were all performed to elucidate its mechanism. Additionally, in order to understand how ß-Elemene and FLT3 interact, molecular docking, molecular dynamics simulations, and computational ADME investigations were performed. RESULTS: ß-Elemene exhibited cytotoxic activity against FLT3-mutated MV4-11 and FLT3 wild-type THP-1 cells, with an IC50 of around 25 µg/ml. The molecular studies revealed that ß-Elemene inhibited cell proliferation by inducing p53, and the involvement of p21, p27, HTRA, and HSPs were also demonstrated. The interactive inhibition in proliferation was confirmed via molecular docking and dynamics analyses. ß-Elemene occupied the FLT3 enzymatic pocket with good stability at the FLT3 active site. CONCLUSIONS: We concluded from our observations that ß-Elemene causes cell death in ITD mutant AML cells, together with the effects of stress factors and inhibiting cell division.