Formulation Development and Evaluation of Nanoparticles Entrapping Begonia medicinalis Extract Using PLGA/Sodium Alginate/Polyvinyl Alcohol Composite Polymer for Immunomodulation and Inhibiting 3Cl-SARS-CoV-2 Protease
Keywords:
Begonia medicinalis, PLGA, Nanoparticles, Immunomodulation, Inhibition, SARS-CoV-2 Protease
Abstract
The study explores the formulation of nanoparticles containing Begonia medicinalis extract using a blend of PLGA (Poly-Lactic-co-Glycolic Acid), sodium alginate, and polyvinyl alcohol. This formulation aimed to investigate its physicochemical properties and potential immunomodulatory and anti-SARS-CoV-2 activities. Immunomodulation was evaluated through phagocytosis activity measurement, TNF-α, and IFN-γ levels, while anti-SARS-CoV-2 activity was assessed through in vitro testing on the SARS-CoV-2 protease enzyme. Nanoparticles were prepared via the solvent evaporation method with various PLGA:alginate:PVA ratios (1:3:3, 1:3:6, 1:6:3, and 1:6:6). Characterization included organoleptic examination, particle size measurement (179.3-250.7 nm), thermal degradation at 190°C, and analysis of phytochemical content (phenolic, flavonoid, and saponin total) ranging from 18.66-21.028 mg GAE/g, 1.862-2.492 mg QE/g, and 191.975-307.897 mg EE/g, respectively. The formulations exhibited notable immune-stimulating effects by increasing phagocytotic percentage and TNF-α/IFN-γ levels and demonstrated inhibitory activity against SARS-CoV-2 3Cl protease enzyme. The encapsulation efficiency (EE) for phenolic, flavonoid, and saponin fell within the ranges of 17-19%, 16-22%, and 60-96%, respectively. Among the formulations, nanoparticle 3 (1:6:3) emerged as the optimal choice due to its superior physicochemical attributes. This particular nanoparticle exhibited immune-stimulating properties and inhibited the SARS-CoV-2 virus, suggesting its potential application in SARS-CoV-2 treatment. In conclusion, nanoparticle formulation 3 (1:6:3) displayed promising characteristics, showcasing immunomodulatory effects and anti-SARS-CoV-2 activity. This research paves the way for potential therapeutic interventions against SARS-CoV-2 using nanoparticle-based B. medicinalis extract formulations.
References
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Lim, M. P. (2015). Core-shell structure alginate-PLGA/PLLA microparticles as a novel drug delivery system for water soluble drugs [Nanyang Technological University]. https://doi.org/10.32657/10356/62178
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Mardiyanto. (2016). Preparation and Characterization of Submicron Particles of PLGA Incorporating Rifampin Using Emulsion Solvent Diffusion. Proceeding - ICB Pharma II “Current Breakthrough in Pharmacy Materials and Analyses.”
Mir, M., Ahmed, N., & Rehman, A. U. (2017). Recent applications of PLGA based nanostructures in drug delivery. Colloids and Surfaces B: Biointerfaces, 159, 217–231. https://doi.org/10.1016/j.colsurfb.2017.07.038
Mohanraj, V. J., & Chen, Y. (2007). Nanoparticles—A review. Tropical Journal of Pharmaceutical Research, 5(1), 561–573. https://doi.org/10.4314/tjpr.v5i1.14634
Nguyen, K. Q., Scarlett, C. J., & Vuong, Q. V. (2021). Assessment and comparison of phytochemicals and antioxidant properties from various parts of the Australian maroon bush (Scaevola spinescens). Heliyon, 7(4), e06810. https://doi.org/10.1016/j.heliyon.2021.e06810
Nurcholis, W., Sya’bani Putri, D. N., Husnawati, H., Aisyah, S. I., & Priosoeryanto, B. P. (2021). Total flavonoid content and antioxidant activity of ethanol and ethyl acetate extracts from accessions of Amomum compactum fruits. Annals of Agricultural Sciences, 66(1), 58–62. https://doi.org/10.1016/j.aoas.2021.04.001
Operti, M. C., Bernhardt, A., Grimm, S., Engel, A., Figdor, C. G., & Tagit, O. (2021). PLGA-based nanomedicines manufacturing: Technologies overview and challenges in industrial scale-up. International Journal of Pharmaceutics, 605, 120807. https://doi.org/10.1016/j.ijpharm.2021.120807
Panigrahi, D., Sahu, P. K., Swain, S., & Verma, R. K. (2021). Quality by design prospects of pharmaceuticals application of double emulsion method for PLGA loaded nanoparticles. SN Applied Sciences, 3(6), 638. https://doi.org/10.1007/s42452-021-04609-1
Rivera-Hernández, G., Antunes-Ricardo, M., Martínez-Morales, P., & Sánchez, M. L. (2021). Polyvinyl alcohol based-drug delivery systems for cancer treatment. International Journal of Pharmaceutics, 600, 120478. https://doi.org/10.1016/j.ijpharm.2021.120478
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Salatin, S., Barar, J., Barzegar-Jalali, M., Adibkia, K., Kiafar, F., & Jelvehgari, M. (2017). Development of a nanoprecipitation method for the entrapment of a very water soluble drug into Eudragit RL nanoparticles. Research in Pharmaceutical Sciences, 12(1), 1–14. https://doi.org/10.4103/1735-5362.199041
Silva, M. F., Hechenleitner, A. A. W., Irache, J. M., Oliveira, A. J. A. D., & Pineda, E. A. G. (2015). Study of Thermal Degradation of PLGA, PLGA Nanospheres and PLGA/Maghemite Superparamagnetic Nanospheres. Materials Research, 18(6), 1400–1406. https://doi.org/10.1590/1516-1439.045415
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Sulastri, E., Zubair, M. S., Anas, N. I., Abidin, S., Hardani, R., Yulianti, R., & Aliyah A, A. (2018). Total Phenolic, Total Flavonoid, Quercetin Content and Antioxidant Activity of Standardized Extract of Moringa oleifera Leaf from Regions with Different Elevation. Pharmacognosy Journal, 10(6s), s104–s108. https://doi.org/10.5530/pj.2018.6s.20
Takeuchi, I., Kato, Y., & Makino, K. (2021). Effects of Polyvinyl Alcohol on Drug Release from Nanocomposite Particles Using Poly (L-lactide-co-glycolide). Journal of Oleo Science, 70(3), 341–348. https://doi.org/10.5650/jos.ess20299
Warsito, W., Noorhamdani, N., Sukardi, S., & Dwi Susanti, R. (2017). MICROENCAPSULATION OF Cytrus hystrix OIL AND ITS ACTIVITY TEST AS AN ANTIMICROBIAL AGENT. Journal of Enviromental Engineering and Sustainable Technology, 4(2), 131–137. https://doi.org/10.21776/ub.jeest.2017.004.02.9
Zhang, H., Cheng, J., & Ao, Q. (2021). Preparation of Alginate-Based Biomaterials and Their Applications in Biomedicine. Marine Drugs, 19(5), 264. https://doi.org/10.3390/md19050264
Zubair, M., Maulana, S., Widodo, A., Pitopang, R., Arba, M., & Hariono, M. (2021). GC-MS, LC-MS/MS, Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from Zingiber officinale Roscoe. Molecules, 26(17), 5230. https://doi.org/10.3390/molecules26175230
Zubair, M. S., Alarif, W. M., Ghandourah, M. A., & Anam, S. (2021). A new steroid glycoside from Begonia sp.: Cytotoxic activity and docking studies. Natural Product Research, 35(13), 2224–2231. https://doi.org/10.1080/14786419.2019.1669026
Zubair, M. S., Khairunisa, S. Q., Sulastri, E., Ihwan, null, Widodo, A., Nasronudin, null, & Pitopang, R. (2021). Antioxidant and antiviral potency of Begonia medicinalis fractions. Journal of Basic and Clinical Physiology and Pharmacology, 32(4), 845–851. https://doi.org/10.1515/jbcpp-2020-0476
Zubair, M. S., Syamsidi, A., Sulastri, E., Widyasari, N., Sanjaya, I. P., & Pakaya, D. (2022). Immunomodulatory Activity of Benalu Batu (Begonia Medicinalis) Ethanolic Extract In Experimental Animals. Indonesian Journal of Pharmacy, Article in Press. https://doi.org/doi.org/10.22146/ijp.3588
Anam, S., Ritna, A., Dwimurti, F., Rismayanti, D., & Zubair, M. S. (2014). Aktivitas Sitotoksik Ekstrak Metanol Benalu Batu (Begonia sp.): Ethnomedicine Suku Wana Sulawesi Tengah. Jurnal Ilmu Kefarmasian Indonesia, 12(1), 10–16.
Annisa, R., Fauziyah, B., Megawati, D. S., & Zahrah, F. (2023). Formulation of Silver Nanoparticle Mouthwash and Testing of Antibacterial Activity Against Staphylococcus aureus. Journal of Tropical Pharmacy and Chemistry, 7(2), 52–58. https://doi.org/10.25026/jtpc.v7i2.386
Anonim. (2012). NANOCOMPOSIX’S GUIDE TO DYNAMIC LIGHT SCATTERING MEASUREMENT AND ANALYSIS. NANOCOMPOSIX’S.
Aryal, S., Baniya, M. K., Danekhu, K., Kunwar, P., Gurung, R., & Koirala, N. (2019). Total Phenolic Content, Flavonoid Content and Antioxidant Potential of Wild Vegetables from Western Nepal. Plants, 8(4), 96. https://doi.org/10.3390/plants8040096
Babick, F. (2020). Dynamic light scattering (DLS). In Characterization of Nanoparticles (pp. 137–172). Elsevier. https://doi.org/10.1016/B978-0-12-814182-3.00010-9
Chand, N., & Vashishtha, S. R. (2000). Development, structure and strength properties of PP/PMMA/FA blends. Bulletin of Materials Science, 23(2), 103–107. https://doi.org/10.1007/BF02706550
Chaplin, D. D. (2010). Overview of the immune response. Journal of Allergy and Clinical Immunology, 125(2), S3–S23. https://doi.org/10.1016/j.jaci.2009.12.980
Chua, L. S., Lau, C. H., Chew, C. Y., & Dawood, D. A. S. (2019). Solvent Fractionation and Acetone Precipitation for Crude Saponins from Eurycoma longifolia Extract. Molecules, 24(7), 1416. https://doi.org/10.3390/molecules24071416
Dang, Y., & Guan, J. (2020). Nanoparticle-based drug delivery systems for cancer therapy. Smart Materials in Medicine, 1, 10–19. https://doi.org/10.1016/j.smaim.2020.04.001
Gaaz, T., Sulong, A., Akhtar, M., Kadhum, A., Mohamad, A., & Al-Amiery, A. (2015). Properties and Applications of Polyvinyl Alcohol, Halloysite Nanotubes and Their Nanocomposites. Molecules, 20(12), 22833–22847. https://doi.org/10.3390/molecules201219884
Han, F. Y., Thurecht, K. J., Whittaker, A. K., & Smith, M. T. (2016). Bioerodable PLGA-Based Microparticles for Producing Sustained-Release Drug Formulations and Strategies for Improving Drug Loading. Frontiers in Pharmacology, 7. https://doi.org/10.3389/fphar.2016.00185
Hernández-Giottonini, K. Y., Rodríguez-Córdova, R. J., Gutiérrez-Valenzuela, C. A., Peñuñuri-Miranda, O., Zavala-Rivera, P., Guerrero-Germán, P., & Lucero-Acuña, A. (2020). PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: Effects of formulation parameters. RSC Advances, 10(8), 4218–4231. https://doi.org/10.1039/C9RA10857B
Hoa, L. T. M., Chi, N. T., Nguyen, L. H., & Chien, D. M. (2012). Preparation and characterisation of nanoparticles containing ketoprofen and acrylic polymers prepared by emulsion solvent evaporation method. Journal of Experimental Nanoscience, 7(2), 189–197. https://doi.org/10.1080/17458080.2010.515247
Hodoroaba, V.-D., Rades, S., Salge, T., Mielke, J., Ortel, E., & Schmidt, R. (2016). Characterisation of nanoparticles by means of high-resolution SEM/EDS in transmission mode. IOP Conference Series: Materials Science and Engineering, 109, 012006. https://doi.org/10.1088/1757-899X/109/1/012006
Kirti, & Khora, S. S. (2022). Alginate: A Promising Biopolymer in Drug Delivery System. In S. Jana & S. Jana (Eds.), Marine Biomaterials (pp. 61–95). Springer Nature Singapore. https://doi.org/10.1007/978-981-16-4787-1_3
Liechty, W. B., Kryscio, D. R., Slaughter, B. V., & Peppas, N. A. (2010). Polymers for drug delivery systems. Annual Review of Chemical and Biomolecular Engineering, 1, 149–173. https://doi.org/10.1146/annurev-chembioeng-073009-100847
Lim, M. P. (2015). Core-shell structure alginate-PLGA/PLLA microparticles as a novel drug delivery system for water soluble drugs [Nanyang Technological University]. https://doi.org/10.32657/10356/62178
Lin, C.-W., Tsai, F.-J., Tsai, C.-H., Lai, C.-C., Wan, L., Ho, T.-Y., Hsieh, C.-C., & Chao, P.-D. L. (2005). Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Research, 68(1), 36–42. https://doi.org/10.1016/j.antiviral.2005.07.002
Mardiyanto. (2016). Preparation and Characterization of Submicron Particles of PLGA Incorporating Rifampin Using Emulsion Solvent Diffusion. Proceeding - ICB Pharma II “Current Breakthrough in Pharmacy Materials and Analyses.”
Mir, M., Ahmed, N., & Rehman, A. U. (2017). Recent applications of PLGA based nanostructures in drug delivery. Colloids and Surfaces B: Biointerfaces, 159, 217–231. https://doi.org/10.1016/j.colsurfb.2017.07.038
Mohanraj, V. J., & Chen, Y. (2007). Nanoparticles—A review. Tropical Journal of Pharmaceutical Research, 5(1), 561–573. https://doi.org/10.4314/tjpr.v5i1.14634
Nguyen, K. Q., Scarlett, C. J., & Vuong, Q. V. (2021). Assessment and comparison of phytochemicals and antioxidant properties from various parts of the Australian maroon bush (Scaevola spinescens). Heliyon, 7(4), e06810. https://doi.org/10.1016/j.heliyon.2021.e06810
Nurcholis, W., Sya’bani Putri, D. N., Husnawati, H., Aisyah, S. I., & Priosoeryanto, B. P. (2021). Total flavonoid content and antioxidant activity of ethanol and ethyl acetate extracts from accessions of Amomum compactum fruits. Annals of Agricultural Sciences, 66(1), 58–62. https://doi.org/10.1016/j.aoas.2021.04.001
Operti, M. C., Bernhardt, A., Grimm, S., Engel, A., Figdor, C. G., & Tagit, O. (2021). PLGA-based nanomedicines manufacturing: Technologies overview and challenges in industrial scale-up. International Journal of Pharmaceutics, 605, 120807. https://doi.org/10.1016/j.ijpharm.2021.120807
Panigrahi, D., Sahu, P. K., Swain, S., & Verma, R. K. (2021). Quality by design prospects of pharmaceuticals application of double emulsion method for PLGA loaded nanoparticles. SN Applied Sciences, 3(6), 638. https://doi.org/10.1007/s42452-021-04609-1
Rivera-Hernández, G., Antunes-Ricardo, M., Martínez-Morales, P., & Sánchez, M. L. (2021). Polyvinyl alcohol based-drug delivery systems for cancer treatment. International Journal of Pharmaceutics, 600, 120478. https://doi.org/10.1016/j.ijpharm.2021.120478
Robertson, G. P., & Paul, E. A. (2000). Decomposition and Soil Organic Matter Dynamics. In O. E. Sala, R. B. Jackson, H. A. Mooney, & R. W. Howarth (Eds.), Methods in Ecosystem Science (pp. 104–116). Springer New York. https://doi.org/10.1007/978-1-4612-1224-9_8
Salatin, S., Barar, J., Barzegar-Jalali, M., Adibkia, K., Kiafar, F., & Jelvehgari, M. (2017). Development of a nanoprecipitation method for the entrapment of a very water soluble drug into Eudragit RL nanoparticles. Research in Pharmaceutical Sciences, 12(1), 1–14. https://doi.org/10.4103/1735-5362.199041
Silva, M. F., Hechenleitner, A. A. W., Irache, J. M., Oliveira, A. J. A. D., & Pineda, E. A. G. (2015). Study of Thermal Degradation of PLGA, PLGA Nanospheres and PLGA/Maghemite Superparamagnetic Nanospheres. Materials Research, 18(6), 1400–1406. https://doi.org/10.1590/1516-1439.045415
Stankovic, M. S., Niciforovic, N., Topuzovic, M., & Solujic, S. (2011). Total Phenolic Content, Flavonoid Concentrations and Antioxidant Activity, of The Whole Plant and Plant Parts Extracts from Teucrium Montanum L. Var. Montanum , F. Supinum (L.) Reichenb. Biotechnology & Biotechnological Equipment, 25(1), 2222–2227. https://doi.org/10.5504/BBEQ.2011.0020
Strambeanu, N., Demetrovici, L., Dragos, D., & Lungu, M. (2015). Nanoparticles: Definition, Classification and General Physical Properties. In M. Lungu, A. Neculae, M. Bunoiu, & C. Biris (Eds.), Nanoparticles’ Promises and Risks (pp. 3–8). Springer International Publishing. https://doi.org/10.1007/978-3-319-11728-7_1
Sulastri, E., Zubair, M. S., Anas, N. I., Abidin, S., Hardani, R., Yulianti, R., & Aliyah A, A. (2018). Total Phenolic, Total Flavonoid, Quercetin Content and Antioxidant Activity of Standardized Extract of Moringa oleifera Leaf from Regions with Different Elevation. Pharmacognosy Journal, 10(6s), s104–s108. https://doi.org/10.5530/pj.2018.6s.20
Takeuchi, I., Kato, Y., & Makino, K. (2021). Effects of Polyvinyl Alcohol on Drug Release from Nanocomposite Particles Using Poly (L-lactide-co-glycolide). Journal of Oleo Science, 70(3), 341–348. https://doi.org/10.5650/jos.ess20299
Warsito, W., Noorhamdani, N., Sukardi, S., & Dwi Susanti, R. (2017). MICROENCAPSULATION OF Cytrus hystrix OIL AND ITS ACTIVITY TEST AS AN ANTIMICROBIAL AGENT. Journal of Enviromental Engineering and Sustainable Technology, 4(2), 131–137. https://doi.org/10.21776/ub.jeest.2017.004.02.9
Zhang, H., Cheng, J., & Ao, Q. (2021). Preparation of Alginate-Based Biomaterials and Their Applications in Biomedicine. Marine Drugs, 19(5), 264. https://doi.org/10.3390/md19050264
Zubair, M., Maulana, S., Widodo, A., Pitopang, R., Arba, M., & Hariono, M. (2021). GC-MS, LC-MS/MS, Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from Zingiber officinale Roscoe. Molecules, 26(17), 5230. https://doi.org/10.3390/molecules26175230
Zubair, M. S., Alarif, W. M., Ghandourah, M. A., & Anam, S. (2021). A new steroid glycoside from Begonia sp.: Cytotoxic activity and docking studies. Natural Product Research, 35(13), 2224–2231. https://doi.org/10.1080/14786419.2019.1669026
Zubair, M. S., Khairunisa, S. Q., Sulastri, E., Ihwan, null, Widodo, A., Nasronudin, null, & Pitopang, R. (2021). Antioxidant and antiviral potency of Begonia medicinalis fractions. Journal of Basic and Clinical Physiology and Pharmacology, 32(4), 845–851. https://doi.org/10.1515/jbcpp-2020-0476
Zubair, M. S., Syamsidi, A., Sulastri, E., Widyasari, N., Sanjaya, I. P., & Pakaya, D. (2022). Immunomodulatory Activity of Benalu Batu (Begonia Medicinalis) Ethanolic Extract In Experimental Animals. Indonesian Journal of Pharmacy, Article in Press. https://doi.org/doi.org/10.22146/ijp.3588
Published
2025-01-17
How to Cite
Zubair, M. S., Afriano, R., Ihwan, I., Syamsidi, A., & Sulastri, E. (2025). Formulation Development and Evaluation of Nanoparticles Entrapping Begonia medicinalis Extract Using PLGA/Sodium Alginate/Polyvinyl Alcohol Composite Polymer for Immunomodulation and Inhibiting 3Cl-SARS-CoV-2 Protease. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.12150
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