Author(s):
D. Herawati, P. Pudjiastuti, A.H. Zaidan, E. Hendradi
Email(s):
pratiwi-p@fst.unair.ac.id
DOI:
10.52711/0974-360X.2025.00357 
Address:
D. Herawati1,2, P. Pudjiastuti2*, A.H. Zaidan3, E. Hendradi4
1Department of Medical Laboratory Technology, Faculty of Health Sciences, Universitas Maarif Hasyim Latif, Sidoarjo, Indonesia.
2Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Surabaya, Indonesia.
3Department of Physics, Faculty of Science and Technology, Universitas Airlangga, Surabaya, Indonesia.
4Department of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.
*Corresponding Author
Published In:
Volume - 18,
Issue - 6,
Year - 2025
ABSTRACT:
Fucoidan (F) is an anticancer potential natural compound extracted from the brown seaweed Sargassum plagiophyllum. However, poor solubility and lack of targeted delivery are major drawbacks in its therapeutic application. The aim of this study is to enhance the delivery and efficacy of fucoidan by encapsulating it using ?-carrageenan (C) and Carrageenan folate (Cf) as carrier matrices. The particle size of the resulting fucoidan-loaded nanocapsules with ?-Carrageenan (F-CNPs) and ?-Carrageenan folate (F-CfNPs), were 84.2?12.1nm and 93.2?10.7nm, respectively. Encapsulation Efficiency (EE) was high, with 92.34?0.58% for F-CNPs and 95.41? 0.06% for F-CfNPs, while the Loading amount (LA) were 46.17?0.29% and 47.70?0.03%, respectively. Anticancer activities of the nanocapsules against HeLa and MCF-7 cell lines were performed. The IC50 values in F-CfNPs were significantly lower compared with F-CNPs, representing increased efficacy due to the addition of the targeting folate group. In HeLa cells, the IC50 values were 33.13?4.53?g ml-1 for F-CNPs, 21.14?3.59 ?g ml-1 for F-CfNPs, and 3.16?3.56 ?g ml-1 for doxorubicin. While, in MCF-7 cells, the IC50 values were 30,56?3.86 ?g ml-1 for F-CNPs, 24.92?3.83?g ml-1 for F-CfNPs, and 15.79?2.84?g ml-1 for doxorubicin. These results clearly indicated that the fucoidan nanocapsules acted as a potent therapeutic against HeLa and MCF.7 cell lines. However, F-CfNPs showed higher efficiency among the fabricated NPs due to higher cellular uptake. This study toward the 14th Sustainable Development Goals (SDG) by utilizing brown seaweed to enhance its economic value and aligns with the 3rd SDG goal of ensuring good health well-being through improvements in cancer treatment.
Cite this article:
D. Herawati, P. Pudjiastuti, A.H. Zaidan, E. Hendradi. K-Carrageenan Folate Nanoencapsulation of Fucoidan from Sargassum plagiophyllum and Anticancer Activity Enhancement. Research Journal of Pharmacy and Technology. 2025;18(6):2501-7. doi: 10.52711/0974-360X.2025.00357
Cite(Electronic):
D. Herawati, P. Pudjiastuti, A.H. Zaidan, E. Hendradi. K-Carrageenan Folate Nanoencapsulation of Fucoidan from Sargassum plagiophyllum and Anticancer Activity Enhancement. Research Journal of Pharmacy and Technology. 2025;18(6):2501-7. doi: 10.52711/0974-360X.2025.00357 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-6-10
REFERENCES:
1. Bray F. Laversanne M. Sung H. Ferlay J. Siegel RL Soerjomataram IJ. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024. doi.org/10.3322/caac.21834.
2. Jose S. and Balakrishnan BR. Cervical Cancer Prevention and Treatment: An Overview. Res J Pharm Technol. 2021; 14(4): 2353-9. doi.org/10.52711/0974-360X.2021.00415
3. Akshara R. Gokul RM. Sathiavelu A. Mythili S. Marine environment: A potential source for anticancer drugs. Research J. Pharm. and Tech. 2017; 10(5): 1543–50. doi.org/10.5958/0974-360X.2017.00272.4
4. He. X. Xue M. Jiang S. Li W. Yu J. Xiang S. Fucoidan promotes apoptosis and inhibits EMT of breast cancer cells. Biol Pharm Bull. 2019; 42(3): 442–7. doi.org/10.1248/bpb.b18-00777
5. Catrawardhana P. Saharso ER. Mushlih Y. Hapsari Y. Fadilah F. Phytochemistry and Cytotoxicity Analysis of Kemang (Mangifera kemanga) Fruit Extract on HeLa Cervical Cancer Cell Line. Res J Pharm Technol. 2022; 15(4): 1721–6. doi.org/10.52711/0974-360X.2022.00288
6. Lin Y. Qi X. Liu H. Xue K. Xu S. Tian Z. The anti-cancer effects of fucoidan: a review of both in vivo and in vitro investigations. Cancer Cell Int. 2020; 20(1): 154. doi.org/10.1186/s12935-020-01233-8
7. Narayani SS. Saravanan S. Ravindran J. Ramasamy MS. Chitra. In vitro anticancer activity of fucoidan extracted from Sargassum cinereum against Caco-2 cells. Int. J. Biol. Macromol. 2019; 138: 618–28. doi.org/10.1016/j.ijbiomac.2019.07.127
8. Lai Y-H. Chiang C-S. Hsu C-H. Cheng H-W. Chen S-Y. Development and Characterization of a Fucoidan-Based Drug Delivery System by Using Hydrophilic Anticancer Polysaccharides to Simultaneously Deliver Hydrophobic Anticancer Drugs. Biomolecules. 2020; 10(7): 970. doi.org/10.3390/biom10070970
9. Umamahesvari, H. Fabrication and Character Study of the Anticancer Drug Paclitaxel (Taxol): PLGA nanoparticles - The benefaction for the modern therapeutic area. Research J. Pharm. and Tech. 2020; 13(1): 265–9. doi.org/10.5958/0974-360X.2020.00054.2
10. Shetty V. Jakhade A. Shinde K. Chikate R. Kaul-Ghanekar R. Folate mediated targeted delivery of cinnamaldehyde loaded and FITC functionalized magnetic nanoparticles in breast cancer: In vitro, in vivo and pharmacokinetic studies. New Journal of Chemistry. 2021; 45(8): 1500–15. doi.org//10.1002/jps.20457
11. Hilgenbrink AR. and Low PS. Folate receptor-mediated drug targeting: From therapeutics to diagnostics. J Pharm Sci. 2005; 94: 2135–46. doi.org//10.1002/jps.20457
12. Pillai JJ. Thulasidasan AKT. Anto RJ. Devika NC. Ashwanikumar N. Kumar GSV. Curcumin entrapped folic acid conjugated PLGA-PEG nanoparticles exhibit enhanced anticancer activity by site specific delivery. RSC Adv. 2015; 5: 25518–24. doi.org/10.1039/c5ra00018a
13. Sudimack J. and Lee RJ. Targeted drug delivery via the folate receptor. Adv Drug Deliv Rev. 2000; 41(2):147–62. doi.org/10.1016/S0169-409X(99)00062-9
14. Hossen S. Hossain MK. Basher MK. Mia MNH. Rahman MT. Smart nanocarrier-based drug delivery systems for cancer therapy and toxicity studies: A review. J Adv Res. 2018; 15:1–18. doi.org/10.1016/j.jare.2018.06.005
15. Choudhury A. Laskar R. Deka D. Sonowal K. Saha S. Dey B. A Review on Nanoparticle: Types, Preparation and its Characterization. Research J. Pharm. and Tech. 2021; 14(3): 1815–22. doi.org/10.5958/0974-360X.2021.00322X
16. Venkateswara Rao S. and Sathesh Kumar S. Nanocarrier Based Anticancer Drug Delivery System: Current Trends and Prospects. Research J. Pharm. and Tech. 2017; 10(1): 330–6. doi.org/10.5958/0974-360X.2017.00067.1
17. Mizrahy S. and Peer D. Polysaccharides as building blocks for nanotherapeutics. Chem Soc Rev. 2012; 41(7): 2623–40. doi.org/10.1039/c1cs15239d
18. Patil, R. Y., Patil, S. A., Chivate, N. D. and Patil, Y. N. Herbal Drug Nanoparticles: Advancements in Herbal Treatment. Research J. Pharm. and Tech. 2011; 11: 421–6. doi.org/10.1039/c1cs15239d
19. Herawati D. Pudjiastuti P Zaidan AH. Hendradi E. Wafiroh S. Fucoidan from Sargassum plagiophyllum by Microwave Assisted Extraction in Comparison with Conventional Methods. Rasayan Journal of Chemistry. 2022; 15(4): 2959–63. doi.org/10.31788/RJC.2022.1547035
20. Herawati D. Pudjiastuti P. Zaidan A. Hendradi E. Sucipto T. Monosaccharides Composition of Fucoidan from Brown Seaweed (Sargassum plagiophyllum) and the Corresponding Antidengue Activity. Egypt J Chem. 2024; 67(7): 23-29. doi.org/10.21608/EJCHEM.2023.242019.8735
21. Wardana AP. Aminah NS. Fahmi MZ. Kristanti AN. Haninda ZI. Yoshiaki T. Choudhary MI. Nanoencapsulation of Syzygium polycephalum Extract Using Folate Modified κ-Carrageenan as Vehicles for Pronounced Anticancer Activity. Journal of Natural Product Research. 2020; 4(11): 945–52. doi.org/10.26538/tjnpr/v4i11.17
22. Chiang CS. Huang BJ. Chen JY. Chieng WW. Lim SH. Lee W. Shyu W-C. Jeng LB.. Fucoidan-Based Nanoparticles with Inherently Therapeutic Efficacy for Cancer Treatment. Pharmaceutics. 2021; 13: 1986. doi.org/10.3390/pharmaceutics13121986
23. Sasikala M. Sundaraganapathy R. Mohan S. MTT Assay on Anticancer Properties of Phytoconstituents from Ipomoea aquatica forsskal using MCF–7 cell lines for breast cancer in Women. Research J. Pharm. and Tech. 2020; 13(3): 1356–60. doi.org/10.5958/0974-360X.2020.00250.4
24. Yuan Y. and Macquarrie D. Microwave assisted extraction of sulfated polysaccharides (fucoidan) from Ascophyllum nodosum and its antioxidant activity. Carbohydr Polym. 2015; 129: 101–107. doi.org/10.1016/j.carbpol.2015.04.057
25. Rodriguez-Jasso RM. Mussatto SI. Pastrana L. Aguilar CN. Teixeira JA. Microwave-assisted extraction of sulfated polysaccharides (fucoidan) from brown seaweed. Carbohydr Polym. 2011; 86(3): 1137–44. doi.org/10.1016/j.carbpol.2011.06.00
26. Ren B. Chen C. Li C. Fu X. You L. Liu R.H. Optimization of microwave-assisted extraction of Sargassum thunbergii polysaccharides and its antioxidant and hypoglycemic activities. Carbohydr. Polym. 2017; 173: 192–201. doi.org/10.1016/j.carbpol.2017.05.094
27. Vaquero M-G. Ummat V. Tiwari B. Rajauria G. Exploring Ultrasound, Microwave and Ultrasound–Microwave Assisted Extraction Technologies to Increase the Extraction of Bioactive Compounds and Antioxidants from Brown Macroalgae. Mar Drugs. 2020; 18(3):172. doi.org/10.3390/md18030172
28. Dobrinčić A. Balbino S. Zoric Z. Pedisić S. Kovačević DK. Garofulić IE. Dragović-Uzelac V. Advanced Technologies for the Extraction of Marine Brown Algal Polysaccharides. Mar Drugs. 2020; 18(3):168. doi.org/10.3390/md18030168
29. Shofia SI. Jayakumar K. Mukherjee A. Chandrasekaran N. Efficiency of brown seaweed (: Sargassum longifolium) polysaccharides encapsulated in nanoemulsion and nanostructured lipid carrier against colon cancer cell lines HCT 116. RSC Adv. 2018; 8(29):15973–84. doi.org/10.1039/c8ra02616e
30. Suresh V. Anbazhagan C. Thangam R. Senthilkumar D. Senthilkumar N. Kannan S. Rengasamy R. Palani P. Stabilization of mitochondrial and microsomal function of fucoidan from Sargassum plagiophyllum in diethylnitrosamine induced hepatocarcinogenesis. Carbohydr. Polym. 2013; 92(2): 1377–85. doi.org/10.1016/j.procbio.2012.12.014
31. Artemisia R. Setyowati EP. Martien R. Nugroho AK. The properties of brown marine algae Sargassum turbinarioides and Sargassum ilicifolium collected From Yogyakarta, Indonesia. Indonesian Journal of Pharmacy. 2019; 30(1): 43–51. doi.org/10.14499/indonesianjpharm30iss1pp43
32. Tsakos M. Schaffert ES. Clement LL. Villadsen NL. Poulsen TB. Ester coupling reactions–an enduring challenge in the chemical synthesis of bioactive natural products. Nat Prod Rep. 2015; 32: 605–32. doi.org/10.1039/C4NP00106K
33. Fahmi MZ. and Chang, JY. A facile strategy to enable nanoparticles for simultaneous phase transfer, folate receptor targeting, and cisplatin delivery. RSC Adv. 2014; 4: 56713–21. doi.org/10.1039/c4ra11582a
34. Haggag YA. Elrahman AAA. Ulber R. Zayed A. Fucoidan in Pharmaceutical Formulations: A Comprehensive Review for Smart Drug Delivery Systems. Mar Drugs. 2023; 21(2). doi.org/10.3390/md21020112
35. Mishra A. and Yadav SK. Development of sustained release metoprolol succinate matrix tablets using kappa carrageenan as monolithic polymer. Research J. Pharm. and Tech. 2016; 9(9): 1311–6. doi.org/0.5958/0974-360X.2016.00249.3
36. Lowilius W. Brenda CE. Risya AR. Nurma NA. Rafika IP. Erni HP. Fadilah F. Isolation, Synthesis Nanoparticle, and In-vitro test of Pinostrobin from Kaempferia pandurata on MCF-7 and MDAMB-231 Breast Cancer Cell. Research J. Pharm. and Tech. 2020; 13(6):2797–801. doi.org/ 10.5958/0974-360X.2020.00497.7
37. Choi DG. Venkatesan J. Shim MS. Selective Anticancer Therapy Using Pro-Oxidant Drug-Loaded Chitosan–Fucoidan Nanoparticles. Int J Mol Sci. 2019; 20(13): 3220. doi.org/10.3390/ijms20133220
38. Herawati D. Hendradi E. Zaidan AH. Pudjiastuti P. Microwave-Assisted Extraction of Fucoidan from Sargassum plagiophyllum and its Activities. Pak J Biol Sci. 2022; 25(11): 1008–13. doi.org/0.3923/pjbs.2022.1008.1013.
39. Parker N. Turk MJ. Westrick E. Lewis JD. Low PS. Leamon CP. Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem. 2005; 338(2): 284–93. doi.org/10.1016/j.ab.2004.12.02
40. Fernández M. Javaid F. Chudasama V. Advances in targeting the folate receptor in the treatment/imaging of cancers. Chem Sci. 2018; 9(4): 790–810. doi.org/10.1039/C7SC04004K