Background
The cardiovascular hazards associated with radiotherapy have become a major issue. Statins have been shown to improve the survival rate and hinder the cardiovascular harm in cancer patients exposed to radiotherapy.
Objective
The current study attempted to evaluate the efficacy of rosuvastatin (ROSU) loaded in bilosomes (BLs) drug carrier, as a new formulation to mitigate the cardiovascular deteriorations induced by radiation exposure in experimental rats.
Materials and methods
Rosuvastatin loaded bilosomes (ROSU-BLs) were prepared using the thin film hydration technique. Characterization of the prepared formulations was performed by several approaches. The in vitro release profile was carried out using dialysis bag diffusion technique. In the experimental in vivo phase, rats were exposed to γ-radiation (7 Gy) and treated with ROSU either free or formulated form to evaluate their redox, anti-hyperlipidemic, anti-inflammatory and anti-apoptotic activities.
Results and conclusion
The results revealed the efficient development of ROSU-BLs, which exhibited entrapment efficiency (EE%) varying from 65.47% to 86.87%, particle sizes in nanosized range from 247.4 to 414 nm, negatively charged zeta potential and transmission electron microscopy (TEM) verified the conventional sphere-shaped vesicles. In vitro release study revealed biphasic pattern with extended release of ROSU up to 24 h. In vivo results showed the advantage of ROSU-BLs compared to free ROSU in enhancing cardiac redox activity by restoring the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) levels, while concurrently diminishing the levels of tumor necrosis factor-alpha (TNF-α) and caspase-9 in cardiac tissue. Such impact was also verified by histopathological investigations. In conclusion, the current data indicate the efficacy of bilosomes carrier in improving the oral delivery of ROSU, reflected by the enhanced potential of ROSU-BLs to mitigate the cardiovascular deteriorations induced by γ-radiation via activating the cardiac redox Nrf2/HO-1 system with consequent suppression of pro-inflammatory and pro-apoptotic markers.