Abstract
beta-sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of beta-sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing beta-sitosterol encapsulated Alginate/Chitosan nanoparticles (beta-sito-Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 +/- 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of beta-sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of beta-sito-Alg/Ch/NPs was also studied. The pharmacokinetic parameters including C-max, T-max, half-life (t(1/2)), and bioavailability were measured for beta-sito-Alg/Ch/NPs as compared to 13-sito-suspension. The beta-sito-Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 +/- 6% vs. 11 +/- 1% from beta-sito-Alg/Ch/NPs and beta-sito-suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 +/- 9% vs. 12 +/- 4% drug release from beta-sito-Alg/Ch/NPs and beta-sito-suspension. When compared to the beta-sito-suspension, the beta-sito-Alg/Ch/NPs demonstrated greater cytotoxicity (p < 0.05) and similar to 3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that beta-sito-Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the beta-sito-suspension.