"Exploring the Potential of Ferulic Acid loaded Nanostructured Lipid Carriers: Angiotensin Inhibition via Docking, Formulation, and Pharmacokinetic and Pharmacodynamics Studies".

Ferulic acid (FA) is a phenolic compound obtained naturally and is a versatile antioxidant identified for its potential in managing hypertension. However, its application is constrained due to its classification as a BCS Class IV moiety. To address this, we concentrated on improving its solubility and permeability by developing nanostructured lipid carriers (NLCs) of FA using emulsification probe sonication technique. Lipids stearic acid and Labrasol, surfactant Tween 80, and sonication time were adopted for the formulation studies, with optimization utilizing Box-Behnken design. The FA-NLCs were evaluated for particle size, zeta potential, PDI, entrapment efficiency, and in vitro release. Pharmacokinetic and intestinal uptake studies were carried out on male Wistar rats. Pharmacodynamic studies were performed using the high fructose diet model for hypertension in Sprague Dawley rats.In-silico studies, exposed a strong interaction between FA and ACE receptor (1UZF), with docking score of -7.144 kcal/mol and binding energy of -54.624 kcal/mol. Optimized formulation (F12 FA-NLC) established a particle size of 103.4 ± 8.89 nm, zeta potential of -43.6 mV, polydispersity index of 0.531 ± 0.021, and entrapment efficiency of 88.90 ± 6.27%. In-vitro release studies displayed, that plain FA released 103.13 ± 8.80% within 4 hours, whereas, FA-NLCs released 40.34 ± 5.35% drug after 24 hours indicating sustained release.Pharmacokinetic studies of FA-NLC showed a 2.6-fold increase in C and a 1.9-fold increase in AUC and half-life compared to pure Intestinal uptake results emphasized significant lymphatic uptake via clathrin-mediated endocytosis, bypassing first-pass metabolism, thus, improving therapeutic efficacy. Therefore, the study concluded that FA-NLC effectively reduced blood pressure as compared to plain FA.