Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity
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(et...
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MDPI AG
2018-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/10/4/232 |
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| author | Moses Andima Gabriella Costabile Lorenz Isert Albert J. Ndakala Solomon Derese Olivia M. Merkel |
| author_facet | Moses Andima Gabriella Costabile Lorenz Isert Albert J. Ndakala Solomon Derese Olivia M. Merkel |
| author_sort | Moses Andima |
| collection | DOAJ |
| description | 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. |
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| language | English |
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| spelling | doaj.art-bbbfcbbf76eb49eab5ddb12fee2fb83e2022-12-22T04:01:14ZengMDPI AGPharmaceutics1999-49232018-11-0110423210.3390/pharmaceutics10040232pharmaceutics10040232Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor ActivityMoses Andima0Gabriella Costabile1Lorenz Isert2Albert J. Ndakala3Solomon Derese4Olivia M. Merkel5Department of Pharmacy, Pharmaceutical Technology & Biopharmaceutics, Ludwig-Maximilian University of Munich, Butenandtstr. 5-13, 81377 Munich, GermanyDepartment of Pharmacy, Pharmaceutical Technology & Biopharmaceutics, Ludwig-Maximilian University of Munich, Butenandtstr. 5-13, 81377 Munich, GermanyDepartment of Pharmacy, Pharmaceutical Technology & Biopharmaceutics, Ludwig-Maximilian University of Munich, Butenandtstr. 5-13, 81377 Munich, GermanyDepartment of Chemistry, University of Nairobi, P.O. Box 30197-00100, Nairobi, KenyaDepartment of Chemistry, University of Nairobi, P.O. Box 30197-00100, Nairobi, KenyaDepartment of Pharmacy, Pharmaceutical Technology & Biopharmaceutics, Ludwig-Maximilian University of Munich, Butenandtstr. 5-13, 81377 Munich, Germanyβ-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.https://www.mdpi.com/1999-4923/10/4/232β-SitosterolPLGA nanoparticlesPEG-PLA nanoparticlesbreast cancer |
| spellingShingle | Moses Andima Gabriella Costabile Lorenz Isert Albert J. Ndakala Solomon Derese Olivia M. Merkel Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity Pharmaceutics β-Sitosterol PLGA nanoparticles PEG-PLA nanoparticles breast cancer |
| title | Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity |
| title_full | Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity |
| title_fullStr | Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity |
| title_full_unstemmed | Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity |
| title_short | Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity |
| title_sort | evaluation of β sitosterol loaded plga and peg pla nanoparticles for effective treatment of breast cancer preparation physicochemical characterization and antitumor activity |
| topic | β-Sitosterol PLGA nanoparticles PEG-PLA nanoparticles breast cancer |
| url | https://www.mdpi.com/1999-4923/10/4/232 |
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