Response surface optimization of a cardioprotective compound through pharmacosomal drug delivery system: in vivo bioavailability and cardioprotective activity potential

Vanillic acid (VA) is a phenolic compound with potential antioxidant activity, which improves ischemia-induced myocardial degeneration, by reducing oxidative stress; however, it suffers poor bioavailability owing to its poor solubility. VA-loaded pharmacosomes were optimized using a central composite design, where the effect of phosphatidylcholine:VA molar ratio and the precursor concentration were studied. An optimized formulation (O-1) was prepared and tested for the release rate of VA, in vivo bioavailability, and cardioprotective potential on myocardial infarction-induced rats. The optimized formulation showed a particle size of 229.7 nm, polydispersity index of 0.29, and zeta potential of - 30 mV. O-1 showed a sustained drug release for 48 h. The HPLC-UV method was developed for the determination of VA in plasma samples using protein precipitation. The optimized formulation showed a great improvement in the bioavailability as compared to VA. The residence time of the optimized formula was 3 times longer than VA. The optimized formulation showed a more potent cardioprotective effect as compared to VA, via inhibition of the MAPK pathway with subsequent inhibition of PI3k/NF-?B signaling, in addition to its antioxidant effect. The optimized formulation showed normalization of many oxidative stress and inflammatory biomarkers. Thus, a VA-loaded pharmacosome formulation with promising bioavailability and cardioprotective activity potential was prepared.

Automated summary

An optimized formulation of vanillic acid-loaded pharmacosomes with promising bioavailability and cardioprotective activity potential was prepared. This formulation showed sustained release and longer residence time compared to vanillic acid, and exhibited a more potent cardioprotective effect through inhibition of the MAPK pathway and PI3k/NF-κB signaling.