Abstract
Natural bioactive compounds, like beta-carotene (beta C), are widely recommended as pharmaceutical supplements that are meant to aid in the treatment of diseases such as cardiovascular diseases. However, extreme hydrophobic nature, chemical instability, and low bioavailability of beta C limit its clinical application. The purpose of this study was to synthesize and characterize silica nanoparticles (SiNPs) and beta C-loaded silica nanoparticles (beta C-SiNPs), and then study its activity as an antihypertensive agent in an experimental animal model. The sol-gel method was utilized in the preparation of SiNPs using different solvent systems. The loading of beta C was accomplished through an in situ-loading method. The physicochemical characterization of obtained SiNPs was carried out to obtain information about morphology, average particle size, chemical integrity, thermal properties, and colloidal stability. In addition, the encapsulation efficiency (EE%) and release profile in either simulated gastric fluid or in physiological conditions were also investigated. The antihypertensive activity was evaluated in NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rat model. The results showed that the sol-gel synthesis SiNPs exhibited a spherical shape nanoparticle with an average size of 122 +/- 38 nm for methanol/water mixture and 598 +/- 123 nm for ethanol/water mixture. However, the sample with 0.05 g beta C content revealed less average particle size (103 +/- 22 nm) with a high EE% of 86%. The encapsulation efficiency (EE %) ranged from 36.4 to 86.8% according to the loading method and beta C content. In addition, the drug release studies showed two distinct release steps due to initial burst effect followed by a controlled release. Indeed, the lowest dose of (beta C-SiNPs) exhibited ameliorative effects against L-NAME-induced hypertension in adult male Wistar rats. Heart tissues and blood were obtained after rats were administered L-NAME and/or beta C-SiNPs orally for 2 weeks for additional histological and biochemical studies. The results revealed that L-NAME therapy resulted in significant cardiac pathological damage as well as a rise in heart function analyses as serum LDH and creatine kinase (CK-MB). In conclusion, nanostructured vehicles (i.e., silica NPs) could be a promising strategy for controlling release of hydrophobic bioactive compounds in pharmaceutical industry and act as antihypertensive agent by restoring biochemical parameters and the histopathological changes in cardiac muscles.