Ulcerative colitis (UC) is a chronic inflammatory colon disorder. Several modern medicines have been used for UC treatment but are associated with side effects. Hence, herbal medicine–inspired lead molecules are promising for managing UC. Chlorogenic acid (CGA), an herbal bioactive, has been reported for anti-inflammatory, anticancer, antioxidant, and immunomodulatory activity. The current study aimed to develop enteric-coated mucoadhesive beads of CGA for colon targeting. CGA-loaded beads were prepared using chitosan and carrageenan as polymers through an ionic gelation technique. Furthermore, beads were coated with Eudragit S-100. The formulations were characterized by particle size analyzer, ultraviolet (UV)-spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and in vitro drug release study. The optimized formulation (CGA-F2) showed particle size (440.6 ± 6.1 μm), zeta potential (−31.12 ± 2.16 mV), entrapment efficiency (83.56 ± 5.46), %yield (86.87 ± 4.19), and drug loading (1.14 ± 0.09). SEM indicated that the morphologies of CGA-F2 were spherical and ellipsoidal. The FTIR study confirmed the compatibility of the drug with polymers used in the formulations. CGA-F2 exhibited mucoadhesive efficiency (94.33 ± 2.1%) and swelling index (0.98 ± 0.03) at simulated colonic fluid (SCF) pH 7.4 (***p < 0.001) significantly. In an in vitro drug release study, CGA-F2 (95.07 ± 3.85%) showed a sustained drug release profile in SCF (pH 7.4) at 37 ± 0.5°C for 24 h. Optimized formulation exhibited drug release in a sustained manner for 24 h, which may be due to the effect of mucoadhesive and enteric coating polymer. Hence, CGA-loaded beads would be promising for treating the UC.
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References
1.
NambuR, MuiseAM. Advanced understanding of monogenic inflammatory bowel disease. Front Pediatr, 2020; 8:618918; doi: 10.3389/fped.2020.618918
2.
AxelradJE, LichtigerS, YajnikV. Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment. World J Gastroenterol, 2016; 22(20):4794–4801; doi: 10.3748/wjg.v22.i20.4794
3.
KaplanGG. The global burden of IBD: From 2015 to 2025. Nat Rev Gastroenterol Hepatol, 2015; 12(12):720–727; doi: 10.1038/nrgastro.2015.150
4.
OlénO, AsklingJ, SachsMC, et al.Mortality in adult-onset and elderly-onset IBD: A nationwide register-based cohort study 1964-2014. Gut, 2020; 69(3):453–461; doi: 10.1136/gutjnl-2018-317572
5.
GajendranM, LoganathanP, JimenezG, et al.A comprehensive review and update on ulcerative colitis. Dis Mon, 2019; 65(12):100851; doi: 10.1016/j.disamonth.2019.02.004
6.
CrossRK. Safety considerations with the use of corticosteroids and biologic therapies in mild-to-moderate ulcerative colitis. Inflamm Bowel Dis, 2017; 23(10):1689–1701; doi: 10.1097/mib.0000000000001261
7.
HirtenRP, IacucciM, ShahS, et al.Combining biologics in inflammatory bowel disease and other immune mediated inflammatory disorders. Clin Gastroenterol Hepatol, 2018; 16(9):1374–1384; doi: 10.1016/j.cgh.2018.02.024
8.
GaoC, ZhouY, ChenZ, et al.Turmeric-derived nanovesicles as novel nanobiologics for targeted therapy of ulcerative colitis. Theranostics, 2022; 12(12):5596–5614; doi: 10.7150/thno.73650
9.
FriesW, DemarzoMG, NavarraG, et al.Ulcerative colitis in adulthood and in older patients: Same disease, same outcome, same risks? Drugs Aging, 2022; 39(6):441–452; doi: 10.1007/s40266-022-00943-0
10.
LiX, LuC, YangY, et al.Site-specific targeted drug delivery systems for the treatment of inflammatory bowel disease. Biomed Pharmacother, 2020; 129:110486; doi: 10.1016/j.biopha.2020.110486
11.
HarwanshRK, ChauhanS, DeshmukhR, et al.Recent insight into herbal bioactives-based novel approaches for chronic intestinal inflammatory disorders therapy. Curr Pharm Biotechnol, 2024; 25(14):1835–1857; doi: 10.2174/0113892010282432231222060355
12.
HarwanshRK, BhatiH, DeshmukhR. Recent updates on the therapeutics benefits, clinical trials, and novel delivery systems of chlorogenic acid for the management of diseases with a special emphasis on ulcerative colitis. Curr Pharm Des, 2024; 30(6):420–439; doi: 10.2174/0113816128295753240129074035
13.
MiaoM, XiangL. Pharmacological action and potential targets of chlorogenic acid. Adv Pharmacol, 2020; 87:71–88; doi: 10.1016/bs.apha.2019.12.002
14.
YanY, LiQ, ShenL, et al.Chlorogenic acid improves glucose tolerance, lipid metabolism, inflammation and microbiota composition in diabetic db/db mice. Front Endocrinol (Lausanne), 2022; 13:1042044; doi: 10.3389/fendo.2022.1042044
15.
ZhangY, ZhuC, ZhaoH, et al.Anti-inflammatory effect of chlorogenic acid in Klebsiella pneumoniae-induced pneumonia by inactivating the p38MAPK pathway. Int J Med Microbiol, 2023; 313(2):151576; doi: 10.1016/j.ijmm.2023.151576
16.
ChauhanS, HarwanshRK. Recent advances in nanocarrier systems for ulcerative colitis: A new era of targeted therapy and biomarker integration. J Drug Deliv Sci Technol, 2024; 93:105466; doi: 10.1016/j.jddst.2024.105466
17.
JuniorAGT, de AraújoJTC, DuarteJL, et al.Polymeric systems for colon-specific mesalazine delivery in the intestinal bowel diseases management. Curr Med Chem, 2023; 30(12):1351–1367; doi: 10.2174/0929867329666220707102912
18.
CurcioC, GrecoAS, RizzoS, et al.Development, optimization and characterization of Eudraguard(®)-based Microparticles for colon delivery. Pharmaceuticals (Basel), 2020; 13(6); doi: 10.3390/ph13060131
19.
Maleki DanaP, HallajzadehJ, AsemiZ, et al.Chitosan applications in studying and managing osteosarcoma. Int J Biol Macromol, 2021; 169:321–329; doi: 10.1016/j.ijbiomac.2020.12.058
20.
Abd El-HackME, El-SaadonyMT, ShafiME, et al.Antimicrobial and antioxidant properties of chitosan and its derivatives and their applications: A review. Int J Biol Macromol, 2020; 164:2726–2744; doi: 10.1016/j.ijbiomac.2020.08.153
21.
StavaracheCE, GhebaurA, DinescuS, et al.5-Aminosalicylic acid loaded chitosan-carrageenan hydrogel beads with potential application for the treatment of inflammatory bowel disease. Polymers (Basel), 2021; 13(15); doi: 10.3390/polym13152463
22.
DeshmukhR, HarwanshRK, PaulSD, et al.Controlled release of sulfasalazine loaded amidated pectin microparticles through Eudragit S 100 coated capsule for management of inflammatory bowel disease. Journal of Drug Delivery Science and Technology, 2020; 55:101495; doi: 10.1016/j.jddst.2019.101495
23.
DeshmukhR, HarwanshRK, RahmanMA. Sodium alginate-guar gum and carbopol based methotrexate loaded mucoadhesive microparticles for colon delivery: An in vitro evaluation. Braz J Pharm Sci, 2021; 57.
24.
DeshmukhR, KumarR. Preformulation considerations development and evaluation of mesalamine loaded polysaccharide-based complex mucoadhesive beads for colon targeting. IJPER, 2021; 55(1):95–106.
25.
SantanaPT, RosasSLB, RibeiroBE, et al.Dysbiosis in inflammatory bowel disease: Pathogenic role and potential therapeutic targets. Int J Mol Sci, 2022; 23(7); doi: 10.3390/ijms23073464
26.
GuoQ, JinY, ChenX, et al.NF-κB in biology and targeted therapy: New insights and translational implications. Signal Transduct Target Ther, 2024; 9(1):53; doi: 10.1038/s41392-024-01757-9
27.
NguyenNTT, MüllerR, BriukhovetskaD, et al.The spectrum of CAR cellular effectors: Modes of action in anti-tumor immunity. Cancers (Basel), 2024; 16(14); doi: 10.3390/cancers16142608
28.
SoaresCLR, WilairatanaP, SilvaLR, et al.Biochemical aspects of the inflammatory process: A narrative review. Biomed Pharmacother, 2023; 168:115764; doi: 10.1016/j.biopha.2023.115764
29.
GiambraV, PagliariD, RioP, et al.Gut microbiota, inflammatory bowel disease, and cancer: The role of guardians of innate immunity. Cells, 2023; 12(22); doi: 10.3390/cells12222654
30.
KaurG, JainS, TiwaryAK. Recent approaches for colon drug delivery. Recent Pat Drug Deliv Formul, 2007; 1(3):222–229; doi: 10.2174/187221107782331665
31.
BelaliN, WathoniN, MuchtaridiM. Advances in orally targeted drug delivery to colon. J Adv Pharm Technol Res, 2019; 10(3):100–106; doi: 10.4103/japtr.JAPTR_26_19
32.
RashidM, KaurV, HallanSS, et al.Microparticles as controlled drug delivery carrier for the treatment of ulcerative colitis: A brief review. Saudi Pharm J, 2016; 24(4):458–472; doi: 10.1016/j.jsps.2014.10.001
33.
PadillaP, EstévezM, AndradeMJ, et al.Proteomics reveal the protective effects of chlorogenic acid on Enterococcus faecium Q233 in a simulated pro-oxidant colonic environment. Food Res Int, 2022; 157:111464; doi: 10.1016/j.foodres.2022.111464
34.
El-MaghawryE, TadrosMI, ElkheshenSA, et al.Eudragit(®)-S100 coated PLGA nanoparticles for colon targeting of Etoricoxib: Optimization and pharmacokinetic assessments in healthy human volunteers. Int J Nanomedicine, 2020; 15:3965–3980; doi: 10.2147/ijn.S244124
35.
ChenL, LiuCS, ChenQZ, et al.Characterization, pharmacokinetics and tissue distribution of chlorogenic acid-loaded self-microemulsifying drug delivery system. Eur J Pharm Sci, 2017; 100:102–108; doi: 10.1016/j.ejps.2017.01.011
36.
KrajewskaJB, PietruszkaP, TomczykD, et al.Evaluation of the effect of liposomes loaded with chlorogenic acid in treatment of 2,4,6-trinitrobenzenesulfonic acid-induced murine colitis. J Physiol Pharmacol, 2019; 70(2); doi: 10.2640/2/jpp.2019.2.10
