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.
Highlights
Beta-sitosterol (β-Sit) is the most abundant plant phytosterol distributed in a wide variety of plant species [1,2]
In vitro release of β-Sit from β-Sit-poly(lactide-co-glycolic acid) (PLGA) and β-Sit-poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) nanoparticles was determined in phosphate-buffered saline (PBS) (PBS, 0.01 M, pH 7.4) and PBS with 0.2% Tween 20
The method was evaluated for precision, linearity, accuracy, limit of detection, and limit of quantitation
Summary
Beta-sitosterol (β-Sit) is the most abundant plant phytosterol distributed in a wide variety of plant species [1,2]. Β-Sit has largely remained a neglected natural product, mostly because of its lower in vitro efficacy as compared to other chemotherapeutic drugs [9] As it is the case with several natural compounds, low aqueous solubility, which translates into low bioavailability, and coupled with low targeting efficacy, has limited clinical development of β-Sit. The use of nanoparticle drug delivery is the objective of several current studies aiming to enhance anticancer therapeutic efficacy of some natural compounds. Cyclodextrins (CD) have been used to enhance the aqueous solubility and bioavailability of β-Sit. For example, several biological evaluations of β-Sit conducted by Awad et al against a panel of cancer cells involved using 2-hydroxypropyl-β-cyclodextrin (HP-βCD) as a carrier vehicle [1,3,4,17]. We hypothesized that encapsulating β-Sit in amphiphilic polymeric nanoparticles can offer better enhancement of anticancer activity against selected cancer-cell lines. The small size of the nanoparticles could potentially help to concentrate the drug at the disease site through the hypothesized enhanced permeability and retention (EPR) effect, enhancing its anticancer efficacy for several folds
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