Surface entrenched ß-sitosterol niosomes for enhanced cardioprotective activity against isoproterenol induced cardiotoxicity in rats.

ABSTRACT

Cardiotoxicity (CT) is a severe condition that negatively impacts heart function. ß-sitosterol (BS) is a group of phytosterols and known for various pharmacological benefits, such as managing diabetes, cardiac protection, and neuroprotection. This study aims to develop niosomes (NS) containing BS, utilizing cholesterol as the lipid and Tween 80 as the stabilizer. The research focuses on designing and evaluating both conventional BS-NS and hyaluronic acid (HA) modified NS (BS-HA-NS) to enhance the specificity and efficacy of BS within cardiac tissue. The resulting niosomal formulation was spherical, with a size of about 158.51 ± 0.57 nm, an entrapment efficiency of 93.56 ± 1.48 %, and a drug loading of 8.07 ± 1.62 %. To evaluate cytotoxicity on H9c2 heart cells, the MTT assay was used. The cellular uptake of BS-NS and BS-HA-NS was confirmed by confocal microscopy on H9c2 cardiac cells. Administering BS-NS and BS-HA-NS intravenously at a dose of 10 mg/kg showed the ability to significantly decrease the levels of cardiac troponin-I (cTn-I), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and lipid peroxidation (MDA). Tissue histopathology indicated a substantial potential for repairing cardiac tissue after treatment with BS-NS and BS-HA-NS and strong cardioprotection against ISO induced myocardial tissue damages. Thus, enhancing BS's therapeutic effectiveness through niosome surface modification holds promise for mitigating cardiac damage resulting from CT.