Ta Thanh Hong , Vo Thanh Khang , Nguyen Thi Kieu My and Nguyen Quoc Chau Thanh *

* Corresponding author (nqcthanh@ctu.edu.vn)

Abstract

PLGA microparticle system loading Nepenthes mirabilis extract (NM/PLGA-NPs) was successfully developed, exhibiting encapsulation efficiency of 12.37%, 70.73% for drug loading, with average particle size of 926 nm. FT-IR spectra and SEM analyses confirmed that the encapsulation process preserved key functional groups and yielded uniform spherical morphology. The system exhibited pH-responsive drug release: rapid release at pH 1.2 and sustained release at pH 6.8 and 7.4, aligning with gastrointestinal transit. Moreover, NM/PLGA-NPs demonstrated prolonged (72-hour) DPPH radical scavenging, indicating a sustained antioxidant effect. Furthermore, cytotoxicity assays on RAW264.7 macrophages revealed biocompatibility and protective cells against H2O2-induced oxidative stress. These findings highlight the therapeutic promise of NM/PLGA-NPs in managing oxidative stress-related disorders.

Keywords: Microparticle, nepenthes mirabilis, oxidation, polyphenol, stress

Tóm tắt

Trong nghiên cứu này, hệ vi hạt PLGA chứa cao chiết từ nắp ấm hoa đôi (Nepenthes mirabilis) (NM/PLGA-NPs) đã được phát triển thành công, với hiệu suất nạp 12,37%, tải 70,73% và kích thước trung bình 926 nm. Kết quả phân tích FT-IR và SEM cho thấy quá trình nạp không làm thay đổi cấu trúc chức năng và duy trì hình thái hình cầu, đồng đều. Hệ vi hạt thể hiện khả năng giải phóng hoạt chất phụ thuộc pH: giải phóng nhanh tại pH 1,2, chậm và ổn định ở pH 6,8 và 7,4, phù hợp với các dạng bào chế theo đường uống. Ngoài ra, hệ NM/PLGA-NPs có khả năng trung hòa gốc tự do DPPH bền vững trong 72 giờ, điều này cho thấy hiệu quả kháng oxy hóa kéo dài. Việc đánh giá độc tính trên tế bào RAW264.7 cho thấy hệ vi hạt an toàn, không gây độc và có khả năng bảo vệ tế bào khỏi tổn thương stress oxy hóa do H2O2. Những kết quả này khẳng định tiềm năng của hệ vi hạt NM/PLGA-NPs trong ứng dụng điều trị các bệnh lý liên quan đến stress oxy hóa.

Từ khóa: Nắp ấm hoa đôi, oxy hóa, polyphenol, stress, vi hạt

Article Details

References

Albisa, A., Piacentini, E., Sebastian, V., Arruebo, M., Santamaria, J., & Giorno, L. (2017). Preparation of Drug-Loaded PLGA-PEG Nanoparticles by Membrane-Assisted Nanoprecipitation. Pharmaceutical Research, 34(6), 1296–1308. https://doi.org/10.1007/S11095-017-2146-Y

Alsaab, H. O., Alharbi, F. D., Alhibs, A. S., Alanazi, N. B., Alshehri, B. Y., Saleh, M. A., Alshehri, F. S., Algarni, M. A., Almugaiteeb, T., Uddin, M. N., & Alzhrani, R. M. (2022). PLGA-Based Nanomedicine: History of Advancement and Development in Clinical Applications of Multiple Diseases. Pharmaceutics, 14(12), 2728. https://doi.org/10.3390/PHARMACEUTICS14122728

Aware, C. B., Patil, D. N., Suryawanshi, S. S., Mali, P. R., Rane, M. R., Gurav, R. G., & Jadhav, J. P. (2022). Natural bioactive products as promising therapeutics: A review of natural product-based drug development. South African Journal of Botany, 151, 512–528. https://doi.org/10.1016/J.SAJB.2022.05.028

Carmona, F., & Pereira, A. M. S. (2013). Herbal medicines: Old and new concepts, truths and misunderstandings. Revista Brasileira de Farmacognosia, 23(2), 379–385. https://doi.org/10.1590/S0102-695X2013005000018

Bộ Y Tế. (2017). Dược điển Việt Nam V.

Chandra, S., Khan, S., Avula, B., Lata, H., Yang, M. H., Elsohly, M. A., & Khan, I. A. (2014). Assessment of Total Phenolic and Flavonoid Content, Antioxidant Properties, and Yield of Aeroponically and Conventionally Grown Leafy Vegetables and Fruit Crops: A Comparative Study. Evidence-Based Complementary and Alternative Medicine, 2014(1), 253875. https://doi.org/10.1155/2014/253875

Chavan, Y. R., Tambe, S. M., Jain, D. D., Khairnar, S. V., & Amin, P. D. (2022). Redefining the importance of polylactide-co-glycolide acid (PLGA) in drug delivery. Annales Pharmaceutiques Françaises, 80(5), 603–616. https://doi.org/10.1016/J.PHARMA.2021.11.009

Drinković, N., Beus, M., Barbir, R., Debeljak, Ž., Tariba, L. B., Kalčec, N., Ćurlin, M., Bekavac, A., Gorup, D., Mamić, I., Mandić, D., Micek, V., Turčić, P., Günday-Türeli, N., Türeli, E., & Vinković, V. I. (2024). Novel PLGA-based nanoformulation decreases doxorubicin-induced cardiotoxicity. Nanoscale, 16(19), 9412–9425. https://doi.org/10.1039/D3NR06269D

Gonzales, C. M., Dalmolin, L. F., da Silva, K. A., Slade, N. B. L., Lopez, R. F. V., Moreto, J. A., & Schwarz, K. (2021). New Insights of Turmeric Extract-Loaded PLGA Nanoparticles: Development, Characterization and In Vitro Evaluation of Antioxidant Activity. Plant Foods for Human Nutrition, 76(4), 507–515. https://doi.org/10.1007/S11130-021-00929-0/METRICS

Goshtasbi, H., Hashemzadeh, N., Fathi, M., Movafeghi, A., Barar, J., & Omidi, Y. (2025). Mitigating oxidative stress toxicities of environmental pollutants by antioxidant nanoformulations. Nano TransMed, 4, 100087. https://doi.org/10.1016/J.NTM.2025.100087

Guo, X., Zuo, X., Zhou, Z., Gu, Y., Zheng, H., Wang, X., Wang, G., Xu, C., & Wang, F. (2023). PLGA-Based Micro/Nanoparticles: An Overview of Their Applications in Respiratory Diseases. International Journal of Molecular Sciences, 24(5), 4333. https://doi.org/10.3390/IJMS24054333

Hua, S. (2020). Advances in Oral Drug Delivery for Regional Targeting in the Gastrointestinal Tract - Influence of Physiological, Pathophysiological and Pharmaceutical Factors. Frontiers in Pharmacology, 11, 524. https://doi.org/10.3389/FPHAR.2020.00524

Jadhav, R., Das, J., Rajyaguru, S., Kyada, S., Vaibhav, K.P., Teja, K. D., Bhutia, O. S. & Chauthe, K. (2025). Regulations, current development, and future prospects of phytopharmaceuticals, a new class of herbal medicines in India. Discover Pharmaceutical Sciences, 1(1), 1–31. https://doi.org/10.1007/S44395-025-00006-4

Jomova, K., Alomar, S. Y., Valko, R., Liska, J., Nepovimova, E., Kuca, K., & Valko, M. (2025). Flavonoids and their role in oxidative stress, inflammation, and human diseases. Chemico-Biological Interactions, 413, 111489. https://doi.org/10.1016/J.CBI.2025.111489

Kaplan, M., Öztürk, K., Öztürk, S. C., Tavukçuoğlu, E., Esendağlı, G., & Calis, S. (2023). Effects of Particle Geometry for PLGA-Based Nanoparticles: Preparation and In Vitro/In Vivo Evaluation. Pharmaceutics, 15(1), 175. https://doi.org/10.3390/PHARMACEUTICS15010175

Khiêm, N. H., Khang, V. T., Tuân, N. T., & Thanh, N. Q. C. (2024). Bào chế và đánh giá hoạt tính sinh học của hệ vi hạt PLGA chứa cao chiết lá Hoàn ngọc đỏ (Strobilanthes schomburgkii). Tạp Chí Khoa Học Đại Học Cần Thơ, 60(3), 105–110. https://doi.org/10.22144/CTUJOS.2024.301

Kopustinskiene, D. M., Jakstas, V., Savickas, A., & Bernatoniene, J. (2020). Flavonoids as Anticancer Agents. Nutrients, 12(2), 457. https://doi.org/10.3390/NU12020457

Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., Gargiulo, G., Testa, G., Cacciatore, F., Bonaduce, D., & Abete, P. (2018). Oxidative stress, aging, and diseases. Clinical Interventions in Aging, 13, 757. https://doi.org/10.2147/CIA.S158513

Lu, B., Lv, X., & Le, Y. (2019). Chitosan-Modified PLGA Nanoparticles for Control-Released Drug Delivery. Polymers, 11(2), 304. https://doi.org/10.3390/POLYM11020304

Madani, F., Khosravani, M., & Adabi, M. (2023). PLGA Nanoparticles Loaded with Cinnamon Extract and Coated with PVA/Poloxamer188. Medical Sciences Forum, 20(1), 8. https://doi.org/10.3390/IECC2023-14262

Musuc, A. M., Mititelu, M., Chelu, M., Rossi, F., Visan, A. I., & Negut, I. (2024). Development and Applications of PLGA Hydrogels for Sustained Delivery of Therapeutic Agents. Gels, 10(8), 497. https://doi.org/10.3390/GELS10080497

Nabila, A., Roof, M., James, R. J., Ramli, S., Sritularak, B., Rojsitthisak, P., & Halim, H. (2023). Protection of Fargesin against Hydrogen Peroxide-induced Cell Death in RAW 264.7 Cells. International Journal of Pharmaceutical Investigation, 14(1), 55–61. https://doi.org/10.5530/IJPI.14.1.8

Nguyen, T. Q. C., Hong, T. T., Khang, V. T., Ho Thi Nhu, Y., Pham, D. T., Giao, D. H., Tran, T. T. T., & Kamei, K. (2024). Anti-inflammatory Constituents Isolated From Launaea sarmentosa Against Infection by LPS-stimulated Macrophages. Records of Natural Products, 18(6), 663–673. https://doi.org/10.25135/RNP.487.2410.3343

Öztürk, K., Kaplan, M., & Çalış, S. (2024). Effects of nanoparticle size, shape, and zeta potential on drug delivery. International Journal of Pharmaceutics, 666, 124799. https://doi.org/10.1016/J.IJPHARM.2024.124799

Paiva, A. M., Pinto, R. A., Teixeira, M., Barbosa, C. M., Lima, R. T., Vasconcelos, M. H., Sousa, E., & Pinto, M. (2013). Development of noncytotoxic PLGA nanoparticles to improve the effect of a new inhibitor of p53-MDM2 interaction. International Journal of Pharmaceutics, 454(1), 394–402. https://doi.org/10.1016/J.IJPHARM.2013.07.017

Pereira, M. C., Oliveira, D. A., Hill, L. E., Zambiazi, R. C., Borges, C. D., Vizzotto, M., Mertens-Talcott, S., Talcott, S., & Gomes, C. L. (2018). Effect of nanoencapsulation using PLGA on antioxidant and antimicrobial activities of guabiroba fruit phenolic extract. Food Chemistry, 240, 396–404. https://doi.org/10.1016/J.FOODCHEM.2017.07.144

Shu, Z., Ji, Y., Liu, F., Jing, Y., Jiao, C., Li, Y., Zhao, Y., Wang, G., & Zhang, J. (2024). Proteomics Analysis of the Protective Effect of Polydeoxyribonucleotide Extracted from Sea Cucumber (Apostichopus japonicus) Sperm in a Hydrogen Peroxide-Induced RAW264.7 Cell Injury Model. Marine Drugs, 22(7), 325. https://doi.org/10.3390/MD22070325

Thanh, N. Q. C., Tuệ, T. G., Huỳnh, T. T. D., Thanh, V. N., Khiêm, N. H., Khang, V. T., & Hồng, T. T. (2025). Nghiên cứu tiềm năng kháng ung thư của cao chiết nắp ấm hoa đôi (Nepenthes mirabilis). Tạp Chí Khoa Học Đại Học Cần Thơ, 61(3), 99–107. https://doi.org/10.22144/CTUJOS.2025.083

Thanh, N. V., Thao, N. P., Dat, L. D., Huong, P. T. T., Lee, S. H., Jang, H. D., Cuong, N. X., Nam, N. H., Kiem, P. V., Minh, C. V., & Kim, Y. H. (2015). Two new naphthalene glucosides and other bioactive compounds from the carnivorous plant Nepenthes mirabilis. Archives of Pharmacal Research, 38(10), 1774–1782. https://doi.org/10.1007/s12272-015-0576-9

Thao, N. P., Luyen, B. T. T., Koo, J. E., Kim, S., Koh, Y. S., Thanh, N. V., Cuong, N. X., Kiem, P. V., Minh, C. V., & Kim, Y. H. (2016). In vitro anti-inflammatory components isolated from the carnivorous plant Nepenthes mirabilis (Lour.) Rafarin. Pharmaceutical Biology, 54(4), 588–594. https://doi.org/10.3109/13880209.2015.1067234

Thu, H. P., Quang, D. T., Trang, T. T. M., Ha, H. T. T., Nam, N. H., Phuc, N. X., Nguyet, M., Thong, P. Q., Tuyet, H. T. P., Oanh, K. T. V., & Huong, L. M. (2013). In Vitro Apoptosis Enhancement of Hep-G2 Cells by PLA­TPGS and PLA­PEG Block Copolymer Encapsulated Curcumin Nanoparticles. Chemistry Letters, 42(3), 255–257, https://doi.org/10.1246/cl.2013.255

Todaro, B., Moscardini, A., & Luin, S. (2022). Pioglitazone-Loaded PLGA Nanoparticles: Towards the Most Reliable Synthesis Method. International Journal of Molecular Sciences, 23(5), 2522. https://doi.org/10.3390/IJMS23052522

Ullmann, C., Babick, F., & Stintz, M. (2019). Microfiltration of Submicron-Sized and Nano-Sized Suspensions for Particle Size Determination by Dynamic Light Scattering. Nanomaterials, 9(6), 829. https://doi.org/10.3390/NANO9060829

Vincenzo, S. Di, Ferrante, G., Ferraro, M., Cascio, C., Malizia, V., Licari, A., La Grutta, S., & Pace, E. (2023). Oxidative Stress, Environmental Pollution, and Lifestyle as Determinants of Asthma in Children. Biology, 12(1), 133. https://doi.org/10.3390/BIOLOGY12010133

Watcharadulyarat, N., Rattanatayarom, M., Ruangsawasdi, N., & Patikarnmonthon, N. (2023). PEG–PLGA nanoparticles for encapsulating ciprofloxacin. Scientific Reports, 13(1), 1–11. https://doi.org/10.1038/s41598-023-27500-y

Zhang, Z., & Feng, S. S. (2006). The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)–tocopheryl polyethylene glycol succinate nanoparticles. Biomaterials, 27(21), 4025–4033. https://doi.org/10.1016/J.BIOMATERIALS.2006.03.006