Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity

Abstract

β-Sitosterol (β-Sit) is a dietary phytosterol with demonstrated anticancer activity against a panel of cancers, but its poor solubility in water limits its bioavailability and therapeutic efficacy. In this study, poly(lactide-co-glycolic acid) (PLGA) and block copolymers of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) were used to encapsulate β-Sit into nanoparticles with the aim of enhancing its in vitro anticancer activity. β-Sitosterol-loaded PLGA and PEG-PLA nanoparticles (β-Sit-PLGA and β-Sit-PEG-PLA) were prepared by using a simple emulsion-solvent evaporation technique. The nanoparticles were characterized for size, particle size distribution, surface charge, and encapsulation efficiency. Their cellular uptake and antiproliferative activity was evaluated against MCF-7 and MDA-MB-231 human breast cancer cells using flow cytometry and MTT assays, respectively. β-Sit-PLGA and β-Sit-PEG-PLA nanoparticles were spherical in shape with average particle sizes of 215.0 ± 29.7 and 240.6 ± 23.3 nm, a zeta potential of −13.8 ± 1.61 and −23.5 ± 0.27 mV, respectively, and with narrow size distribution. The encapsulation efficiency of β-Sit was 62.89 ± 4.66 and 51.83 ± 19.72 % in PLGA and PEG-PLA nanoparticles, respectively. In vitro release in phosphate-buffered saline (PBS) and PBS/with 0.2% Tween 20 showed an initial burst release, followed by a sustained release for 408 h. β-Sit-PLGA nanoparticles were generally stable in a protein-rich medium, whereas β-Sit-PEG-PLA nanoparticles showed a tendency to aggregate. Flow cytometry analysis (FACS) indicated that β-Sit-PLGA nanoparticles were efficiently taken up by the cells in contrast to β-Sit-PEG-PLA nanoparticles. β-Sit-PLGA nanoparticles were therefore selected to evaluate antiproliferative activity. Cell viability was inhibited by up to 80% in a concentration range of 6.64–53.08 μg/mL compared to the untreated cells. Taken together, encapsulation of β-Sitosterol in PLGA nanoparticles is a promising strategy to enhance its anticancer activity against breast cancer cells.

β-Sitosterol-loaded solid lipid nanoparticles ameliorate complete Freund’s adjuvant-induced arthritis in rats: involvement of NF-кB and HO-1/Nrf-2 pathway

“…With regard to research work carried out in literature to boost β-sitosterol biopharmaceutical efficiency using nanocarriers, the specific formulation such as PLGA-loaded β-sitosterol nanoparticles (Andima et al., 2018 ). While these discuss formulation exhibited a definite improvement in the drug's biopharmaceutical attributes, the current investigation was undertaken to discuss the significant finding of β-sitosterol-SLNs systematically optimized to enhance the effectiveness of drug therapy against CFA-induced arthritis.…”

Polydatin Encapsulated Poly [Lactic-co-glycolic acid] Nanoformulation Counteract the 7,12-Dimethylbenz[a] Anthracene Mediated Experimental Carcinogenesis through the Inhibition of Cell Proliferation

“…PLGA is one of the most extensively used biodegradable polymers because its hydrolysis leads to endogenous and easily metabolized monomers of lactic acid and glycolic acid [11]. Recent publications suggest that PLGA-NPs functionalized with (i) ß-Sitosterol, a natural phytosterol, (ii) resveratrol, a natural polyphenol, and (iii) tea polyphenols of theaflavin and epigallocatechin-3-gallate [12,13,14] might be potential candidates for cancer treatment. Many studies have revealed that encapsulation of PLGA nanoparticles improves the biocompatibility, tunable mechanical property, and controllable degradation of several chemotherapeutic drugs including paclitaxel, tamoxifen, and anthracyclines.…”

Nanotechnology of Tyrosine Kinase Inhibitors in Cancer Therapy: A Perspective

“…The loading of therapeutic drugs into PLA and PLGA synthetic NPs provides many advantages, such as drug protection from enzymatic degradation and promotion of a sustained release. Recent reports demonstrate that these NPs complexed to anticancer drugs can be used for efficient drug delivery [ 75 ] and for reduced nanotoxicity [ 76 ].…”