Pectin Red Dragon Fruit Peel Pectin-Based Microspheres for Oral Quercetin Delivery: Characterization, Stability Study, Digestion Resistance, and Cytotoxicity Against HeLa Cells
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Keywords:
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Pectin, Quercetin, Microsphere, Stability, Cytotoxicity
Abstract
This study aims to evaluate the potential of red dragon fruit skin pectin to be used as a polymer compared with commercial pectin in the quercetin microsphere. Microspheres were made using the ionic gelation technique. Ten formulas were created, utilizing pectin from red dragon skin extracted with oxalic acid (OA75), citric acid (CA75), acetic acid (AA75), and commercial pectin at 1% and 1.5% concentrations. A gel permeation chromatography test (GPC) was performed to evaluate pectin’s molecule weight. Parameters were assessed, including yield, moisture content (MC), Carr’s Index, Hausner ratio, swelling index, Fourier Transform Infrared Spectroscopy (FTIR), particle size, polydispersity index (PDI), drug loading (DL), encapsulation efficiency (EE), Scanning Electron Microscope (SEM), in vitro drug release, accelerated stability test at a temperature of 40±2oC and RH 75±5% for 3 months and thermal stability test in the form of DSC and XRD at the same temperature and humidity for 9 months, digestion resistance with incubation in artificial stomach and intestinal solution for 4 hours continued with cytotoxicity test on HeLa cells with MTT Assays. Results of FTIR indicate a strong interaction between quercetin and pectin in forming a stable microsphere structure; SEM showed the spheres morphologically. The kinetics of quercetin release from microspheres was the Korsmeyer-Peppas model. DL and EE had no significant differences for 3 months and no significant changes in the glass transition in the DSC test during testing until month 9. The FF formulation (1.5% AA75) had the highest cytotoxic activity against HeLa cells and a high Selectivity Index.
References
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Liempepas, A., Rahmadi, M., Ifadotunnikmah, F., Hariyadi, D. M. (2025). Effect of Sodium Alginate–Carrageenan Concentration in Rifampicin Pulmospheres on Physical Characteristics, Release, and Anti-Tuberculosis Activity. Science and Technology Indonesia, 10(3); 817–825
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Nowak, D. and E. & Jakubczyk (2020). The Freeze-Drying of Foods — The Characteristic of the Process Course and the Effect of Its Parameters On. Foods, 9(1488); 1–27
Papp, D., G. Carlström, T. Nylander, M. Sandahl, and C. & Turner (2024). A Complementary Multitechnique Approach to Assess the Bias in Molecular Weight Determination of Lignin by Derivatization-Free Gel Permeation Chromatography. Analytical Chemistry, 96(26); 10612–10619
Purwanti, T., R. A. Satriawan, and D. M. & Hariyadi (2020). The Effect of the Comparison of Sodium Alginate–Gelatin Levels on Microspheres Characteristics (Produced by Ionic Gelation Method Aerosolized Technique). International Journal of Drug Delivery Technology, 10(2); 301–306
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Barnossi, A. El, Moussaid, F., Housseini, A. I. (2021). Tangerine, Banana and Pomegranate Peels Valorisation for Sustainable Environment: A Review. Biotechnology Reports, 29(e00574); 1–21
Carrillo-Martinez, E. J., Flores-Hernández, F. Y., Salazar-Montes, A. M., Nario-Chaidez, H. F., Hernández-Ortega, L. D. (2024). Quercetin, a Flavonoid with Great Pharmacological Capacity. Molecules, 29(5); 1–31
Chai, A., Schmidt, K., Brewster, G., Xiong, L. S. P., Church, B., Wahl, T., Sadabadi, H., Kumpaty, S., Zhang, W. (2023). Design of Pectin-Based Hydrogel Microspheres for Targeted Pulmonary Delivery. Gels, 9(707); 1–13
Choudhury, N., Meghwal, M., Das, K. (2021). Microencapsulation: An Overview on Concepts, Methods, Properties and Applications in Foods. Food Frontiers, 2(4); 426–442
Corpinot, M. K., Bučar, D.-K. (2019). A Practical Guide to the Design of Molecular Crystals. Crystal Growth & Design, 19(2); 1426–1453
Dranca, F., Oroian, M. (2018). Extraction, Purification and Characterization of Pectin from Alternative Sources with Potential Technological Applications. Food Research International, 113; 327–350
Du, H., Steinacher, M., Borca, C., Huthwelker, T., Murello, A., Stellacci, F., Amstad, E. (2018). Amorphous CaCO₃: Influence of the Formation Time on Its Degree of Hydration and Stability. Journal of the American Chemical Society, 140(43); 14289–14299
Durga, G., Ramesh, D. L., Pandurangan, P., Sunkar, S., Abraham, S., Antony, V. S., Sainandhini, R., Thirumurugan, A., Moovendhan, M. (2025). Sustainable Pectin Extraction: Navigating Industrial Challenges and Opportunities with Fruit By-Products – A Review. Process Biochemistry, 154(April); 234–245
Frent, O. D., Duda-Seiman, D. M., Vicas, L. G., Duteanu, N., Nemes, N. S., Pascu, B., Teusdea, A., Morgovan, C. M., Muresan, M. E., Jurca, T., Pallag, A., Micle, O., Marian, E. (2023). Study of the Influence of the Excipients Used for the Synthesis of Microspheres Loaded with Quercetin: Their Characterization and Antimicrobial Activity. Coatings, 13(1376); 1–22
Hayakawa, K., De Felice, C., Watanabe, T., Tanaka, T. (1993). High-Recovery Protein Purification by High-Performance Gel-Permeation Chromatography: Application to Human Serum Biotinidase. Journal of Chromatography B: Biomedical Sciences and Applications, 616(2); 327–332
Helmy, A. M., Elsabahy, M., Abd-Elkareem, M., Ibrahim, E. A., Soliman, G. M. (2020). High-Payload Chitosan Microparticles for the Colonic Delivery of Quercetin: Development and In Vivo Evaluation in a Rabbit Colitis Model. Journal of Drug Delivery Science and Technology, 58(101832); 1–11
Huang, Y., Stonehouse, A., Abeykoon, C. (2023). Encapsulation Methods for Phase Change Materials – A Critical Review. International Journal of Heat and Mass Transfer, 200(123458); 1–73
Jing, S., Chen, H., Liu, E., Zhang, M., Zeng, F., Shen, H. (2023). Oral Pectin/Oligochitosan Microspheres for Colon-Specific Controlled Release of Quercetin to Treat Inflammatory Bowel Disease. Carbohydrate Polymers, 316(121025); 1–15
Joseph, V. M., Rovina, K., Ling, F. W. X., Supri, S., Yin, K. W. (2024). Value-Added Applications of Fruit Peel Biowaste: A Review of Potential Uses in the Food Industry. Food Biophysics, 19; 807–832
Kalalo, T., Miatmoko, A., Tanojo, H., Erawati, T., Hariyadi, D. M., Rosita, N. (2022). Effect of Sodium Alginate Concentration on Characteristics, Stability and Drug Release of Inhalation Quercetin Microspheres. Jurnal Farmasi dan Ilmu Kefarmasian Indonesia, 9(2); 107–114
Kandemir, K., Tomas, M., McClements, D. J., Capanoglu, E. (2022). Recent Advances on the Improvement of Quercetin Bioavailability. Trends in Food Science and Technology, 119; 192–200
Kurniawan, M. F., Hariyadi, D. M., Setyawan, D. (2024a). Optimisation of the Extraction Process of Pectin Polymer from Red Dragon Skin (Hylocereus polyrhizus). Pharmacy Education, 24(3); 116–122
Kurniawan, M. F., Setyawan, D., Hariyadi, D. M. (2024b). Quercetin in Drug Carriers: Polymer Composite, Physical Characteristics, and In Vitro Study. Science and Technology Indonesia, 9(2); 380–412
Lee, S. Y., Ferdinand, V., Siow, L. F. (2022). Effect of Drying Methods on Yield, Physicochemical Properties, and Total Polyphenol Content of Chamomile Extract Powder. Frontiers in Pharmacology, 13(1003209); 1–8
Liempepas, A., Rahmadi, M., Ifadotunnikmah, F., Hariyadi, D. M. (2025). Effect of Sodium Alginate–Carrageenan Concentration in Rifampicin Pulmospheres on Physical Characteristics, Release, and Anti-Tuberculosis Activity. Science and Technology Indonesia, 10(3); 817–825
Liu, Y., Chen, H., Chen, S., Zhang, Y., Zhang, J., Zhu, X., Li, W., Liu, J., Jiang, Y., Li, D. (2023). Pectin-Rich Dragon Fruit Peel Extracts: An Environmentally Friendly Emulsifier of Natural Origin. Food Chemistry, 429(136955); 1–10
Lourenço, S. C., Moldão-Martins, M., Alves, V. D. (2020). Microencapsulation of Pineapple Peel Extract by Spray Drying Using Maltodextrin, Inulin, and Arabic Gum as Wall Matrices. Foods, 9(6); 1–17
Madaniyah, L., Fiddaroini, S., Hayati, E. K., Rahman, M. F., Sabarudin, A. (2025). Stability of Biologically Synthesized Silver Nanoparticles (AgNPs) Using Acalypha indica L. Plant Extract as Bioreductor and Their Potential as Anticancer Agents Against T47D Cells. Science and Technology Indonesia, 10(1); 101–110
Moschona, A. (2018). Encapsulation of Biological Active Phenolic Compounds Extracted from Wine Wastes in Alginate–Chitosan Microbeads. Journal of Microencapsulation, 35(3); 229–240
Nahrowi, R., S. Solehati, W. Widyastuti, N. L. G. R. Juliasih, K. D. Pandiangan, A. Setiawan, and J. & Hendri (2024). New Encapsulation of Fucoxanthin Isolated from Cyclotella Striata by Nano Chitosan–Pectin Using Ionic Gelation Method. Science and Technology Indonesia, 9(3); 517–528
Nalini, T., S. K. Basha, A. M. Sadiq, and V. S. & Kumari (2022). Pectin/Chitosan Nanoparticle Beads as Potential Carriers for Quercetin Release. Materials Today Communications, 33(104172); 1–13
Nowak, D. and E. & Jakubczyk (2020). The Freeze-Drying of Foods — The Characteristic of the Process Course and the Effect of Its Parameters On. Foods, 9(1488); 1–27
Papp, D., G. Carlström, T. Nylander, M. Sandahl, and C. & Turner (2024). A Complementary Multitechnique Approach to Assess the Bias in Molecular Weight Determination of Lignin by Derivatization-Free Gel Permeation Chromatography. Analytical Chemistry, 96(26); 10612–10619
Purwanti, T., R. A. Satriawan, and D. M. & Hariyadi (2020). The Effect of the Comparison of Sodium Alginate–Gelatin Levels on Microspheres Characteristics (Produced by Ionic Gelation Method Aerosolized Technique). International Journal of Drug Delivery Technology, 10(2); 301–306
Putri, A. N., A. K. Soesantyo, and E. D. Iftitah (2025). Effect of Edible Coating Material Composition Based on Chitosan–Gelatin–CaCl₂ and Cinnamon (Cinnamomum verum) Essential Oil on the Protection of Cocoa Beans (Theobroma cacao L.) During Storage. Science and Technology Indonesia, 10(2); 528–537
Ram, M. and E. & Bracci (2024). Waste Management, Waste Indicators and the Relationship with Sustainable Development Goals (SDGs): A Systematic Literature Review. Sustainability, 16(8486); 1–16
Rao, L. (2020). A Review on Quercetin: Assessment of the Pharmacological Potentials and Various Formulations Strategies. International Journal of Pharmaceutical Sciences Review and Research, 64(1); 139–144
Razak, N. A., N. A. S. A. Rahim, A. R. Shaari, and L. Y. & Leng (2020). Effect of Initial Moisture Content on Physical Properties of Orthosiphon stamineus Ground Powder During Storage. IOP Conference Series: Materials Science and Engineering, 932(1); 1–6
Rivas, J. C., L. M. C. Cabral, and M. H. M. da Rocha-Leão (2021). Microencapsulation of Guava Pulp Using Prebiotic Wall Material. Brazilian Journal of Food Technology, 24; 1–11
Rubini, K., E. Boanini, A. Menichetti, F. Bonvicini, G. A. Gentilomi, M. Montalti, and A. & Bigi (2020). Quercetin Loaded Gelatin Films with Modulated Release and Tailored Anti-Oxidant, Mechanical and Swelling Properties. Food Hydrocolloids, 109(106089); 1–9
Saavedra-Leos, M. Z., M. Román-Aguirre, A. Toxqui-Terán, V. Espinosa-Solís, A. Franco-Vega, and C. & Leyva-Porras (2022). Blends of Carbohydrate Polymers for the Co-Microencapsulation of Bacillus clausii and Quercetin as Active Ingredients of a Functional Food. Polymers, 14(236); 1–16
Said, N. S., I. o. Olauyi, and o. Y. & Lee (2023). Pectin Hydrogels: Gel-Forming Behaviors, Mechanisms, and Food Applications. Gels, 9(732); 1–28
Samat, N., M. A. R. Mohamad Roshidi, D. N. A. Don Ramlan Onn, M. A. M. Hatta, and F. A. & Sabaruddin (2025). Synergistic Effects of Double Oxidation on the Extraction and Characterization of Crystalline Nanocellulose from Rattan Waste and Kenaf Fiber. Science and Technology Indonesia, 10(2); 411–419
Sayah, M. Y., R. Chabir, H. Benyahia, Y. R. Kandri, F. O. Chahdi, H. Touzani, and F. & Errachidi (2016). Yield, Esterification Degree and Molecular Weight Evaluation of Pectins Isolated from Orange and Grapefruit Peels under Different Conditions. PLoS One, 11(9); 1–16
Shabir, I., V. Kumar Pandey, R. Shams, A. H. Dar, K. K. Dash, S. A. Khan, I. Bashir, G. Jeevarathinam, A. V. Rusu, T. Esatbeyoglu, and R. & Pandiselvam (2022). Promising Bioactive Properties of Quercetin for Potential Food Applications and Health Benefits: A Review. Frontiers in Nutrition, 9; 1–15
Shah, D. S., K. K. Moravkar, D. K. Jha, V. Lonkar, P. D. Amin, and S. S. Chalikwar (2023). A Concise Summary of Powder Processing Methodologies for Flow Enhancement. Heliyon, 9(e16498); 1–17
Shenoy, P., M. Viau, K. Tammel, F. Innings, J. Fitzpatrick, and L. & Ahrné (2015). Effect of Powder Densities, Particle Size and Shape on Mixture Quality of Binary Food Powder Mixtures. Powder Technology, 272; 165–172
Souza, K. S., L. S. Moreira, B. T. Silva, B. P. M. Oliveira, A. S. Carvalho, P. S. Silva, W. A. Verri, A. B. Sá-Nakanishi, L. Bracht, J. N. Zanoni, O. H. Gonçalves, A. Bracht, and J. F. & Comar (2021). Low Dose of Quercetin-Loaded Pectin/Casein Microparticles Reduces the Oxidative Stress in Arthritic Rats. Life Sciences, 284(119910); 1–11
Sundaram, M. K., R. Raina, N. Afroze, K. Bajbouj, M. Hamad, and A. Haque, S. and & Hussain (2019). Quercetin Modulates Signaling Pathways and Induces Apoptosis in Cervical Cancer Cells. Bioscience Reports, 39(8); 1–17
Yim, S., H. Bian, K. Aoyagi, K. Yamanaka, and A. & Chiba (2023). Effect of Powder Morphology on Flowability and Spreading Behavior in Powder Bed Fusion Additive Manufacturing Process: A Particle-Scale Modeling Study. Additive Manufacturing, 72(103612); 1–20
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Authors
Kurniawan, M. F., Setyawan, D., & Hariyadi, D. M. (2025). Pectin Red Dragon Fruit Peel Pectin-Based Microspheres for Oral Quercetin Delivery: Characterization, Stability Study, Digestion Resistance, and Cytotoxicity Against HeLa Cells. Science and Technology Indonesia, 10(4), 1049–1073. https://doi.org/10.26554/sti.2025.10.4.1049-1073
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