Abstract
Icariin (ICR) is a flavonoid found in plants and possesses cardioprotective, hepatoprotective, antiproliferative, anticancer, and anti-inflammatory properties. Even though ICR has been reported to exhibit therapeutic promise in various preclinical and clinical studies, however, its widespread clinical utility is limited because of low aqueous solubility and low absorption following oral administration. Thus, an enhanced drug delivery system is required to improve therapeutic efficacy and clinical outcome. Hence, this research aimed to develop and explore ICR nanoemulsions (ICR-NE) for improved cardioprotective action against doxorubicin (Dox) induced cardiotoxicity. The critical formulation variables, such as globule size and zeta potential of ICR-NE, were studied using a Box-Behnken response surface design. The improved formulation's globule size and zeta potential were found to be 110.74 nm and −18.45 mV, respectively. Further, thermodynamic stability study showed absence of cracking and phase separation in ICR-NE. Viscosity study reported adequate consistency for oral administration. Additionally, in vitro drug release study showed a sustained release pattern for ICR-NE. The ICR-NE significantly (p < 0.01) restored serum cardiac markers, cardiac tissue antioxidants, and anti-inflammatory markers compared to the free ICR and Dox-treated groups. Compared to the free ICR and Dox-treated group, pretreatment with ICR-NE reduced the expression of Bax and caspase-3, mitigating apoptosis-induced cardiotoxicity. Moreover, pretreatment with ICR-NE significantly reduced the heart weight-body weight ratio histological and fibrotic aberrations towards normal. In conclusion, the current study showed that ICR-NE exhibits a superior cardioprotective effect, possibly due to improved solubility, antioxidant, anti-inflammatory, and anti-apoptotic activity.
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