Epigallocatechin gallate (EGCG), a bioactive compound extracted from green tea, is known for its antioxidant, anti-inflammatory, and anti-obesity effects. However, it is prone to degradation in the gastrointestinal tract due to the alkaline pH and enzymatic activity in the intestine, leading to reduced therapeutic efficacy. To overcome this limitation, EGCG was incorporated into a chitosan-based expandable film designed for prolonged gastric retention and controlled release. Chitosan, a highly swelling polymer, was combined with konjac glucomannan (KGM) as a secondary polymer, along with sodium alginate and glycerin. This system exhibited significant swelling in simulated gastric fluid (pH 1.2), maintaining its expanded structure and achieving a sustained release of over 80% within 8 hours. The inclusion of KGM enhanced the film’s tensile strength, improving its mechanical properties. Bioactivity studies demonstrated that the EGCG-loaded film significantly inhibited inflammation by reducing nitric oxide production in RAW 264.7 macrophage cells. Additionally, it suppressed lipid accumulation on 3T3-L1 adipocytes, supporting its potential anti-obesity effects. These findings suggest that the chitosan–KGM-based expandable film offers an effective gastro-retentive system for EGCG delivery, ensuring prolonged release and enhanced therapeutic benefits.
Lakhiew A, Praparatana R, Sangsen Y, Wiwattanapatapee R. Enhanced oral delivery of epigallocatechin gallate via expanding gastro-retentive films composed of chitosan and konjac glucomannan blends. J Appl Pharm Sci. 2025. Article in Press. http://doi.org/10.7324/JAPS.2025.251914
1. Yang CS, Gang C, Qing W. Recent scientific studies of a traditional Chinese medicine, tea, on prevention of chronic disease. J Tradit Complement Med. 2014;4(1):17–23. doi: http://doi.org/10.4103/2225-4110.12436
2. Chacko SM, Thambi PT, Kuttan R, Nishigaki I. Beneficial effects of green tea: a literature review. Chin Med. 2010;5:13. doi: https://doi.org/10.1186/1749-8546-5-13
3. Baek N, Kim Y, Duncan S, Leitch K, O’Keefe S. (-)-Epigallocatechin gallate stability in ready-to-drink (RTD) green tea infusions in TiO2 and oleic-acid-modified TiO2 polylactic acid film packaging stored under fluorescent light during refrigerated storage at 4 oC. Foods 2021;10:723. doi: http://doi.org/10.3390/foods10040723
4. Kim HS, Quon MJ, Kim JA. New Insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate. Redox Biol. 2014;2:187– 95. doi: http://doi.org/10.1016/j.redox.2013.12.022
5. Casanova E, Salvado J, Crescenti A, Gibert-Ramos A. Epigallocatechin gallate modulates muscle homeostasis in type 2 diabetes and obesity by targeting energetic and redox pathways: a narrative review. Int J Mol Sci. 2019;20(3):532. doi: http://doi.org/10.3390/ijms20030532
6. Hayashi A, Terasaka S, Nukada Y, Kameyama A, Yamane M, Shioi R, et al. 4-Sulfation is the major metabolic pathway of epigallocatechin- 3-gallate in human: characterization of metabolites, enzymatic analysis, and pharmacokinetic profiling. J Agric Food Chem. 2022;70(27):8264–73. doi: http://doi.org/10.1021/acs.jafc.2c02150
7. Vinchurkar K, Sainy J, Khan MA, Mane S, Mishra DK, Dixit P. Features and facts of a gastroretentive drug delivery system – a review. Turk J Pharm Sci. 2022;19(4):476–87. doi: http://doi.org/10.4274/tips.galenos.2021.44959
8. Tripathi J, Thapa P, Maharjan R, Jeong SH. Current state and future perspectives on gastroretentive drug delivery systems. Pharmaceutics 2019;11(4):193. doi: http://doi.org/10.3390/pharmaceutics11040193
9. Ohki T, Ni Q, Ohsako N, Iwamoto M. Mechanical and shape memory behavior of composites with shape memory polymer. Compos Part A Appl Sci Manuf. 2004;35(9):1065–73. doi: http://doi.org/10.1016/j.compositesa.2004.03.001
10. Klausner EA, Lavy E, Friedman M, Hoffman A. Expandable gastroretentive dosage forms. J Control Release. 2003;90(2):143–62. doi: https://doi.org/10.1016/S0168-3659(03)00203-7
11. Vassiliadi E, Aridas A, Schmitt V, Xenakis A, Zoumpanioti M. (Hydroxypropyl)methylcellulose-chitosan film as a matrix for lipase immobilization: operational and morphology study. J Mol Catal. 2022;522:112252. doi: http://doi.org/10.1016/j.mcat.2022.112252
12. Saberian M, Roudsari RS, Haghshenas N, Rousta A, Alizadeh S. How the combination of alginate and chitosan can fabricate a hydrogel with favorable properties for wound healing. Heliyon 2024;10(11):e32040. doi: https://doi.org/10.1016/j.heliyon.2024.e32040
13. Li C, Shang W, Huang Y, Ge J, Ye J, Xin Qu X, et al. Sodium alginate/chitosan composite scaffold reinforced with biodegradable polyesters/gelatin nanofibers for crtilage tissue engineering. Int J Biol Macromol. 2025;285:138054. doi: https://doi.org/10.1016/j.ijbiomac.2024.138054
14. Shuzhen N, Liang J, Hui Z, Yongchao Z, Guigan F, Huining X. Enhancing hydrophobicity, strength and UV shielding capacity of starch film via novel co-cross-linking in neutral conditions. R Soc Open Sci. 2018;5(11):181206. doi: http://doi.org/10.1098/rsos.181206
15. Alonso-Sande M, Teijeiro-Osorio D, Remunan-Lopez C, Alonso MJ.Glucomannan, A Promising polysaccharide for biopharmaceutical purposes. Eur J Pharm Biopharm. 2009;72:453–46. doi: https://doi.org/10.1016/j.ejpb.2008.02.005
16. Zhang C, Chen JD, Yang FQ. Konjac glucomannan, a promising polysaccharide for OCDDS. Carbohydr Polym. 2014;104:175–81. doi: https://doi.org/10.1016/j.carbpol.2013.12.081
17. Ni Y, Liu Y, Zhang W, Shi S, Zhu W, Wang R, et al. Advanced honjac glucomannan-based films in food packaging: classification, preparation, formulation mechanism and function. LWT-Food Sci Technol. 2021;152:112338. doi: https://doi.org/10.1016/j.lwt.2021.112338
18. Chen J, Li X, Chen L, Xie F. Starch film-coated microparticles for oral colon-specific drug delivery. Carbohydr Polym. 2018;191:242– 54. doi: https://doi.org/10.1016/j.carbpol.2018.03.025
19. Thakur R, Pristijono P, Scarlett CJ, Bowyer M, Singh SP, Vuong QV. Starch-based films: major factors affecting their properties. Int J Biol Macromol. 2019;132:1079–89. doi: https://doi.org/10.1016/j.ijbiomac.2019.03.190
20. Akinosho H, Hawkins S, Wicker L. Hydroxypropyl methylcellulose substituent analysis and rheological properties. Carbohydr Polym. 2013;98(1):276–81. doi: https://doi.org/10.1016/j.carbpol.2013.05.081
21. Gökmen FÖ, Bayramgil NP. Preparation and characterization of some cellulose derivatives nanocomposite films. Carbohydr Polym. 2022;297:120030. doi: https://doi.org/10.1016/j.carbpol.2022.120030
22. Laracuente ML, Yu MH, McHugh KJ.Zero-order drug delivery: state of the art and future prospects. J Contr Release. 2020;327:834– 56. doi: https://doi.org/10.1016/j.jconrel.2020.09.020
23. Behera SS, Ray RC. Konjac glucomannan, a promising polysaccharide of Amorphophallus konjac K. koch in health care. Int J Biol Macromol. 2016;92:942–56. doi: https://doi.org/10.1016/j.jibiomac.2016.07.098
24. Jahromi LP, Ghazali M, Ashrafi H, Azadi A. A comparison of models for the analysis of the kinetics of drug release from PLGA-based nanoparticles. Heliyon 2020;6(2):e03451. doi: https://doi.org/10.1016/j.heliyon.2020.e03451
25. Paul DR. Elaborations on the higuchi model for drug delivery. Int J Pharm. 2011;418(1):13–7. doi: https://doi.org/10.1016/j.ijpharm.2010.10.037
26. Zhu W, Long J, Shi M. Release kinetics model fitting of drugs with different structures from viscose fabric. Materials 2023;16(8):3282. doi: https://doi.org/10.3390/ma16083282
27. Singh M, Lee KE, Vinayagam R, Kang SG. Antioxidant and antibacterial profiling of pomegranate-pericarp extract functionalized-zinc oxide nanocomposite. Biotechnol Bioprocess Eng. 2021;26:728–37. doi: http://doi.org/10.1007/s12257-021-0211-1
28. Siripruekpong W, Praparatana R, Issarachot O, Wiwattanapatapee R. Simultaneous delivery of curcumin and resveratrol via in situ gelling, raft-forming, gastroretentive formulations. Pharmaceutics 2024;16:641. doi: http://doi.org/10.3390/pharmaceutics16050641
29. Chen J, Liu C Chen Y, Chen Y, Chang PR. Structural characterization and properties of starch/konjac glucomannan blend films. Carbohydr Polym. 2008;74(4):946–52. doi: http://doi.org/10.1016/j.carbpol.2008.05.021
30. Kaewkroek K, Petchsomrit A, Septama AW, Wiwattanapatapee R. Development of starch/chitosan expandable films as a gastroretentive carrier for ginger extract-loaded solid dispersion. Saudi Pharm J.2022;30(2):120–31. doi: http://doi.org/10.1016/j.jsps.2021.12.017
31. Xu YX, Kim KM, Hanna MA, Nag D. Chitosan–starch composite film: reparation and characterization. Ind Crop Prod. 2005;21(2):185– 92. doi: https://doi.org/10.1016/j.indcrop.2004.03.002
32. Soe MT, Pongjanyakul T, Limpongsa E, Jaipakdee N. Modified glutinous rice starch-chitosan composite films for buccal delivery of hydrophilic drug. Carbohydr Polym. 2020;245:116556. doi: http://doi.org/10.1016/j.carbpol.2020.116556
33. Kraisit P, Limmatvapirat S, Nunthanid J, Sriamornsak P, Luangtana- Anan M. Preparation and characterization of hydroxypropyl methylcellulose/polycarbophil mucoadhesive blend films using a mixture design approach. Chem Pharm Bull. 2017;65(3):284–94. doi: https://doi.org/10.1248/cpb.c16-00849
34. Zanchetta FC, De Wever P, Morari J, Gaspar RC, Prado TP, De Maeseneer T, et al. In vitro and in vivo evaluation of chitosan/HPMC/insulin hydrogel for wound healing applications. Bioengineering 2024;11(2):168. doi: https://doi.org/10.3390/bioengineering11020168
35. Li S, Lyu H, Wang Y, Kong X, Wu X, Zhang L, et al. Two-way reversible shape memory behavior of chitosan/glycerol film triggered by water. Polymer 2023;15:2380. doi: http://doi.org/10.3390/polym15102380
36. Ma S, Zheng Y, Zhou R, Ma M. Characterization of chitosan films incorporated with different substance of konjac glucomannan, cassava starch, maltodextric and gelatin, and application in mongolian cheese packaging. Coatings 2021;11:88. doi: http://doi.org/10.3390/coatings11010084
37. Boontawee R, Issarachot O, Kaewkroek K, Wiwattanapatapee R. Foldable/expandable gastro-retentive films based on starch and chitosan as a carrier for prolonged release of resveratrol. Curr Pharm Biotechnol. 2022;23(7):1009–18. doi: http://doi.org/10.2174/138920 1022666210615115553
38. Llanes L, Dubessay P, Pierre G, Delattre C, Michaud P. Biosourced polysaccharide-based superabsorbents. Polysaccharides 2020;1(1)51– 79. doi: https://doi.org/10.3390/polysaccharides1010005
39. Sivaneswari S, Karthikeyan E, Chandana PJ.Novel expandable gastro retentive system by unfolding mechanism of levetiracetam using simple lattice design – formulation optimization and in vitro evaluation. Bull Fac Pharm Cairo Univ. 2017;55(1):63–72. doi: http://doi.org/10.1016/j.bfopcu.2017.02.003
40. Basak S, Singhal RS. Inclusion of konjac glucomannan in pea protein hydrogels improved the rheological and in vitro release properties of the composite hydrogels. Int J Biol Macromol. 2024;257(2):128689. doi: https://doi.org/10.1016/j.ijbiomac.2023.128689
41. Alvarez-Manceñido F, Landin M, Lacik I, Martínez-Pacheco R. Konjac glucomannan and konjac glucomannan/xanthan gum mixtures as excipients for controlled drug delivery systems. Diffusion of small drugs. Int J Pharm. 2008;349(1–2):11–8. doi: http://doi.org/10.1016/j.ijpharm.2007.07.015
42. Chang SH, Lin YY, Wu GJ, Huang CH, Tsai GJ.Effect of chitosan molecular weight on anti-inflammatory activity in the RAW 264.7 macrophage model. Int J Biol Macromol. 2019;131:167–75. doi: https://doi.org/10.1016/j.ijbiomac.2019.02.066
43. Hossen I, Kaiqi Z, Hua W, Junsong X, Mingquan H, Yanping C. Epigallocatechin gallate (EGCG) inhibits lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells via modulating nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) signaling pathway. Food Sci Nutr. 2023;11(8):4634– 50. doi: https://doi.org/10.1002/fsn3.3427
44. Sun W, Yu Z, Yang S, Jiang C, Kou Y, Xiao L, et al. A transcriptomic analysis reveals novel patterns of gene expression during 3T3-L1 adipocyte differentiation. Front Mol Biosci. 2020;7:564339. doi: http://doi.org/10.3389/fmolb.2020.564339
45. Issarachot O, Bunlung S, Kaewkroek K, Wiwattanapatapee R. Superporous hydrogels based on blends of chitosan and polyvinyl alcohol as a carrier for enhanced gastric delivery of resveratrol. Saudi Pharm J.2023;31(3):335–47. doi: http://doi.org/10.1016/j.jsps.2023.01.001
46. Yuan M, Hu L, Zhu C, Li Q, Tie H, Ruan H, et al. Comparison and assessment of anti-inflammatory and antioxidant capacity between EGCG and phosphatidylcholine-encapsulated EGCG. J Cosmet Dermatol. 2025;24(1):e16628. doi: http://doi.org/10.1111/jocd.16628
47. Wang Y, Li C, Peng W, Sheng J, Zi C, Wu X. EGCG suppresses adipogenesis and promotes browning of 3T3-L1 cells by inhibiting notch1 expression. Molecules 2024;29(11):2555. doi: http://doi.org/10.3390/molecules29112555
48. Lu Y, Chen J, Xian T, Zhou Y, Yuan W, Wang M, et al. Epigallocatechin-3-gallate suppresses differentiation of adipocytes via regulating the phosphorylation of FOXO1 mediated by PI3K-AKT signaling in 3T3-L1 cells. Oncotarget 2017;9(7):7411–23. doi: http://doi.org/10.18632/oncotarget.23590
49. Fungfoung K, Praparatana R Issarachot O, Wiwattanapatapee R. Development of oral in situ gelling liquid formulations of garcinia extract for treating obesity. Gels 2023;9:660. doi: http://doi.org/10.3390/gels9080660
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