Injectable nanocomposite hydrogel of dapagliflozin-CeO₂-loaded polyaniline/hyaluronic acid for suppressing cardiomyocyte oxidative stress in myocardial infarction therapy.

Acute myocardial infarction (AMI) is a prevalent cardiovascular illness that causes mortality worldwide. Cardiac tissue engineering holds significant potential for cardiovascular therapy. The highly branched polyaniline (PANI) and hyaluronic acid (HA) were prepared as a hydrogel that adsorbs CeO2 and dapagliflozin (DAPA) for targeted medication delivery and prolonged release. Furthermore, the composite hydrogel exhibits specific electrical stimulation capabilities due to the incorporation of ceria nanoparticles (CeO2). An AMI rat model was made through ligation of the left anterior descending (LAD) coronary artery. CeO2@PANI/HA and DAPA-CeO2@PANI/HA were injected during ligation and administered for four weeks. Echocardiographic examination revealed that the ejection fraction (EF) of the DAPA-CeO₂@PANI/HA group was considerably enhanced, increasing from 32.42 ± 3.25 in the AMI group to 48.27 ± 2.73 (p < 0.01). The fibrosis level in the DAPA-CeO2@PANI/HA group decreased by 91 % relative to the AMI group. RT-PCR showed upregulation of Nrf2 and HO-1 genes by 4.2-fold and 2.1-fold, respectively, as well as a 66 % reduction in the Bax/Bcl-2 ratio, indicating effective activation of antioxidant pathways and suppression of apoptosis. DAPA-CeO2@PANI/HA improved echocardiographic parameters, decreased signs of myocardial damage, and activated the Nrf2/HO-1 pathway to alleviate oxidative stress and apoptosis, suggesting its cardioprotective potential in AMI.