Vol.:(0123456789) 1 3 BioNanoScience https://doi.org/10.1007/s12668-022-01031-8 Potential of βC‑Loaded Silica Nanoparticles in the Management of L‑NAME –Induced Hypertension in Experimental Rats Mona Wahdan 1  · Emad Tolba 2  · Amr Negm 1  · Fardous F. El‑Senduny 1  · Omali Y. Elkhawaga 1 Accepted: 5 September 2022 © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022 Abstract Natural bioactive compounds, like β-carotene (βC), 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 βC limit its clinical application. The purpose of this study was to synthesize and characterize silica nanoparticles (SiNPs) and βC-loaded silica nanoparticles (βC-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 diferent solvent systems. The loading of βC 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 efciency (EE%) and release profle in either simulated gastric fuid 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 βC content revealed less average particle size (103 ± 22 nm) with a high EE% of 86%. The encapsulation efciency (EE %) ranged from 36.4 to 86.8% according to the loading method and βC content. In addition, the drug release studies showed two distinct release steps due to initial burst efect followed by a controlled release. Indeed, the lowest dose of (βC-SiNPs) exhibited ameliorative efects against L-NAME-induced hypertension in adult male Wistar rats. Heart tissues and blood were obtained after rats were administered L-NAME and/or βC-SiNPs orally for 2 weeks for additional histological and biochemical studies. The results revealed that L-NAME therapy resulted in signifcant 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. Keywords Inorganic drug vesicles · Sol–gel method · β-carotene · Antihypertensive agent · Cardiovascular diseases 1 Introduction Hypertension (HT) is the leading preventable risk factor for incidence of cardiovascular disease. As the population ages and people are exposed to increased lifestyle risk factors, such as smoking, high sodium and low potassium diets, and insufcient physical activity, the prevalence of hypertension rises globally [38]. HT is a rapidly spreading disease with a rising burden and it is related to renal autoregulation impairment or due to a complex interaction between oxidative stress, and endothelial dysfunction [19]. Nitric oxide (NO) has several important functions in most organs in the human body, and long-term blockade of nitric oxide * Emad Tolba emad_nrc@yahoo.com * Omali Y. Elkhawaga elkhawaga70s@mans.edu.eg Mona Wahdan biochemmona@gmail.com Fardous F. El-Senduny fkaneer@mans.edu.ed; fkaneer@mans.edu.eg 1 Chemistry Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt 2 Polymers and Pigments Department, National Research Centre, 33 El Bohouth St, Dokki, Cairo 12311, Egypt