Skip to content
2000
image of Optimized Formulation of Sulfasalazine and Probiotic-Loaded Carrageenan Microparticles Using Design of Experiments for Effective Colitis Management

Abstract

Introduction

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by mucosal inflammation and epithelial barrier dysfunction. Sulfasalazine, a standard anti-inflammatory drug, and probiotics, known for gut microbiota modulation, have both shown efficacy in UC management. However, their combined delivery to the colon remains underexplored. This study aimed to develop a colon-targeted microparticulate formulation containing sulfasalazine and a probiotic strain to enhance anti-inflammatory action and therapeutic effectiveness against UC.

Methods

Microparticles were prepared using a Design of Experiments (DoE) approach, optimizing carrageenan and calcium chloride dihydrate concentrations and stirring speed. The probiotic was co-encapsulated to maintain viability during processing. evaluations included drug release studies and Caco-2 cell line assays for epithelial integrity, ROS generation, and NF-κB expression. efficacy was assessed using an acetic acid-induced colitis model, with evaluations based on inflammation severity, tissue damage and histopathology.

Results

Optimized microparticles ensured sustained sulfasalazine release and preserved probiotic viability. , the formulation improved epithelial barrier function, reduced ROS and pro-inflammatory cytokines, and suppressed NF-κB expression. , treated animals showed significant reduction in colitis severity, improved tissue integrity and better histopathological outcomes compared to controls.

Discussion

The combined sulfasalazine-probiotic microparticles effectively addressed both symptomatic relief and the inflammatory cascade in UC. Probiotics enhanced gut barrier protection, while sustained sulfasalazine release ensured localized therapeutic action. The synergy between drug and probiotic delivery offers a novel approach over conventional therapies.

Conclusion

This study presents a promising colon-targeted microparticulate system combining sulfasalazine and probiotics for effective UC management. The dual-action formulation offers enhanced anti-inflammatory efficacy, reduced tissue damage, and better disease control, supporting its potential in future clinical applications.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/raddf/10.2174/0126673878363141250731125303
2025-08-18
2026-02-03

  • From This Site

    /content/journals/raddf/10.2174/0126673878363141250731125303
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Deshmukh R. Kumari S. Harwansh R.K. Inflammatory bowel disease: A snapshot of current knowledge. Res J Pharm Technol 2020 13 2 956 962 10.5958/0974‑360X.2020.00180.8
    [Google Scholar]
  2. Le Berre C. Honap S. Peyrin-Biroulet L. Ulcerative colitis. Lancet 2023 402 10401 571 584 10.1016/S0140‑6736(23)00966‑2 37573077
    [Google Scholar]
  3. Limdi J.K. Dietary practices and inflammatory bowel disease. Indian J. Gastroenterol. 2018 37 4 284 292 10.1007/s12664‑018‑0890‑5 30209778
    [Google Scholar]
  4. Ananthakrishnan A.N. Higuchi L.M. Huang E.S. Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: A cohort study. Ann. Intern. Med. 2012 156 5 350 359 10.7326/0003‑4819‑156‑5‑201203060‑00007 22393130
    [Google Scholar]
  5. Shahdadi Sardo H. Saremnejad F. Bagheri S. Akhgari A. Afrasiabi Garekani H. Sadeghi F. A review on 5-aminosalicylic acid colon-targeted oral drug delivery systems. Int. J. Pharm. 2019 558 367 379 10.1016/j.ijpharm.2019.01.022 30664993
    [Google Scholar]
  6. Shahdadi Sardou H. Akhgari A. Mohammadpour A.H. Optimization study of combined enteric and time-dependent polymethacrylates as a coating for colon targeted delivery of 5-ASA pellets in rats with ulcerative colitis. Eur. J. Pharm. Sci. 2022 168 106072 10.1016/j.ejps.2021.106072 34774715
    [Google Scholar]
  7. Singh A. Mandal U.K. Narang R.K. Development and characterization of enteric coated pectin pellets containing mesalamine and Saccharomyces boulardii for specific inflamed colon: In vitro and in vivo evaluation. J. Drug Deliv. Sci. Technol. 2021 62 102393 10.1016/j.jddst.2021.102393
    [Google Scholar]
  8. Zhang C. Chen Z. He Y. Oral colon-targeting core–shell microparticles loading curcumin for enhanced ulcerative colitis alleviating efficacy. Chin. Med. 2021 16 1 92 10.1186/s13020‑021‑00449‑8 34551815
    [Google Scholar]
  9. Singh A. Development characterization and evaluation of mesalamine loaded probiotic based microcarriers for the management of ulcerative colitis. MRSPTU: PhD Thesis 2021
    [Google Scholar]
  10. Singh A. Mandal U.K. Narang R.K. Development and in vivo evaluation of pectin based enteric coated microparticles loaded with mesalamine and Saccharomyces boulardii for management of ulcerative colitis. Assay Drug Dev. Technol. 2022 20 1 22 34 10.1089/adt.2021.052 34780287
    [Google Scholar]
  11. Akram W. Garud N. Design expert as a statistical tool for optimization of 5-ASA-loaded biopolymer-based nanoparticles using Box Behnken factorial design. Future J Pharm Sci 2021 7 1 146 10.1186/s43094‑021‑00299‑z
    [Google Scholar]
  12. Tawfeek H.M. Abdel-Aleem J.A. Ahmed M.M. Development and optimization of itopride hydrochloride fast disintegrating tablets using factorial design and response surface methodology. Int. J. Pharm. Sci. Res. 2015 6 4 1661 1672 10.13040/IJPSR.0975‑8232.6(4).1661‑72
    [Google Scholar]
  13. Deshmukh R. Harwansh R.K. Rahman M.A. Sodium alginate-guar gum and carbopol based methotrexate loaded mucoadhesive microparticles for colon delivery: An in vitro evaluation. Braz. J. Pharm. Sci. 2021 57 e19147 10.1590/s2175‑97902020000419147
    [Google Scholar]
  14. Patil A. Pawar P. Gharge V. Doltade U. Doijad R. Mesalamine-loaded mucoadhesive microsphere for colon drug delivery system: Effect of process variables and in vitro characterization. Int. J. Pharm. Investig. 2018 8 2 74 82 10.4103/jphi.JPHI_22_18
    [Google Scholar]
  15. Chawla A. Sharma P. Pawar P. Eudragit S-100 coated sodium alginate microspheres of naproxen sodium: Formulation, optimization and in vitro evaluation. Acta Pharm. 2012 62 4 529 545 10.2478/v10007‑012‑0034‑x 23333888
    [Google Scholar]
  16. Kaur S. Sidhu R. Singh D. Quality by design-steered development of stealth liposomal formulation of everolimus: A systematic optimization and evaluation. Curr. Drug Metab. ••• 25 6 446 464 10.2174/0113892002322171240821104152 39253920
    [Google Scholar]
  17. Javed Ansari M. Soltani A. Ramezanitaghartapeh M. Improved antibacterial activity of sulfasalazine loaded fullerene derivative: Computational and experimental studies. J. Mol. Liq. 2022 348 118083 10.1016/j.molliq.2021.118083
    [Google Scholar]
  18. Vaidya B. Kulkarni N.S. Shukla S.K. Development of inhalable quinacrine loaded bovine serum albumin modified cationic nanoparticles: Repurposing quinacrine for lung cancer therapeutics. Int. J. Pharm. 2020 577 118995 10.1016/j.ijpharm.2019.118995 31935471
    [Google Scholar]
  19. Sinhmar GK Shah NN Rawal SU Chokshi NV Khatri HN Patel BM Surface engineered lipid nanoparticle-mediated site-specific drug delivery system for the treatment of inflammatory bowel disease. Artif Cells Nanomed Biotechnol 2018 46 sup2 565 78 10.1080/21691401.2018.1463232 29661024
    [Google Scholar]
  20. Čalija B. Milić J. Cekić N. Krajišnik D. Daniels R. Savić S. Chitosan oligosaccharide as prospective cross-linking agent for naproxen-loaded Ca-alginate microparticles with improved pH sensitivity. Drug Dev. Ind. Pharm. 2013 39 1 77 88 10.3109/03639045.2012.658813 22339172
    [Google Scholar]
  21. Sinhmar G.K. Shah N.N. Chokshi N.V. Khatri H.N. Patel M.M. Process, optimization, and characterization of budesonide-loaded nanostructured lipid carriers for the treatment of inflammatory bowel disease. Drug Dev. Ind. Pharm. 2018 44 7 1078 1089 10.1080/03639045.2018.1434194 29376433
    [Google Scholar]
  22. Sharma A. Cannoo D.S. A comparative study of effects of extraction solvents/techniques on percentage yield, polyhenolic composition, and antioxidant potential of various extracts obtained from stems of N epeta leucophylla: RP-HPLC-DAD assessment of its polyhenolic constituents. J. Food Biochem. 2017 41 2 e12337 10.1111/jfbc.12337
    [Google Scholar]
  23. Kang R.K. Mishr N. Rai V.K. Guar gum micro-particles for targeted co-delivery of doxorubicin and metformin HCL for improved specificity and efficacy against colon cancer: In vitro and in vivo studies. AAPS PharmSciTech 2020 21 2 48 10.1208/s12249‑019‑1589‑3 31900731
    [Google Scholar]
  24. Shi X. Yan Y. Wang P. In vitro and in vivo study of pH-sensitive and colon-targeting P(LE-IA-MEG) hydrogel microspheres used for ulcerative colitis therapy. Eur. J. Pharm. Biopharm. 2018 122 70 77 10.1016/j.ejpb.2017.10.003 29017953
    [Google Scholar]
  25. Unagolla J.M. Jayasuriya A.C. Drug transport mechanisms and in vitro release kinetics of vancomycin encapsulated chitosan-alginate polyelectrolyte microparticles as a controlled drug delivery system. Eur. J. Pharm. Sci. 2018 114 199 209 10.1016/j.ejps.2017.12.012 29269322
    [Google Scholar]
  26. Arora A. Sharma A. Singh S. Nanoparticles encapsulated in Abelmoschus esculentus polysaccharide-based pellets as colon targeting approach. J. Microencapsul. 2024 41 7 519 534 10.1080/02652048.2024.2390951 39162289
    [Google Scholar]
  27. Singh R. Chandel S. Ghosh A. Glucogallin attenuates the LPS-induced signaling in macrophages and protects mice against sepsis. Int. J. Mol. Sci. 2022 23 19 11254 10.3390/ijms231911254 36232563
    [Google Scholar]
  28. Khan A.N. Singh R. Bhattacharya A. Glucogallin attenuates raw 264.7 cells from arsenic trioxide induced toxicity via the NF-ҡB/NLRP3 pathway. Molecules 2022 27 16 5263 10.3390/molecules27165263 36014502
    [Google Scholar]
  29. Agarwal A. Cho C-L. Esteves S.C. Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation. Asian J. Androl. 2016 18 2 186 193 10.4103/1008‑682X.170441 26732105
    [Google Scholar]
  30. Vatannejad A. Tavilani H. Sadeghi M.R. Amanpour S. Shapourizadeh S. Doosti M. Evaluation of ROS-TAC score and DNA damage in fertile normozoospermic and infertile asthenozoospermic males. Urol. J. 2017 14 1 2973 2978 28116742
    [Google Scholar]
  31. Zhang Y. Khalique A. Du X. Biomimetic design of mitochondria‐targeted hybrid nanozymes as superoxide scavengers. Adv. Mater. 2021 33 9 2006570 10.1002/adma.202006570 33480459
    [Google Scholar]
  32. Han X. Wang R. Song X. Yu F. Lv C. Chen L. A mitochondrial-targeting near-infrared fluorescent probe for bioimaging and evaluating endogenous superoxide anion changes during ischemia/reperfusion injury. Biomaterials 2018 156 134 146 10.1016/j.biomaterials.2017.11.039 29195182
    [Google Scholar]
  33. Gupta R.A. Motiwala M.N. Mahajan U.N. Sabre S.G. Protective effect of Sesbania grandiflora on acetic acid induced ulcerative colitis in mice by inhibition of TNF-α and IL-6. J. Ethnopharmacol. 2018 219 222 232 10.1016/j.jep.2018.02.043 29530609
    [Google Scholar]
  34. Neubauer K. Bednarz-Misa I. Walecka-Zacharska E. Oversecretion and overexpression of nicotinamide phosphoribosyltransferase/pre-B colony-enhancing factor/visfatin in inflammatory bowel disease reflects the disease activity, severity of inflammatory response and hypoxia. Int. J. Mol. Sci. 2019 20 1 166 10.3390/ijms20010166 30621173
    [Google Scholar]
  35. He L.X. Wang J.B. Sun B. Suppression of TNF-α and free radicals reduces systematic inflammatory and metabolic disorders: Radioprotective effects of ginseng oligopeptides on intestinal barrier function and antioxidant defense. J. Nutr. Biochem. 2017 40 53 61 10.1016/j.jnutbio.2016.09.019 27863345
    [Google Scholar]
  36. Fahanik-Babaei J. Baluchnejadmojarad T. Nikbakht F. Roghani M. Trigonelline protects hippocampus against intracerebral Aβ(1–40) as a model of Alzheimer’s disease in the rat: Insights into underlying mechanisms. Metab. Brain Dis. 2019 34 1 191 201 10.1007/s11011‑018‑0338‑8 30421246
    [Google Scholar]
  37. Villanacci V. Reggiani-Bonetti L. Salviato T. Histopathology of IBD Colitis. A practical approach from the pathologists of the Italian Group for the study of the gastrointestinal tract (GIPAD). Pathologica 2021 113 1 39 53 10.32074/1591‑951X‑235 33686309
    [Google Scholar]
  38. McFadden R.M.T. Larmonier C.B. Shehab K.W. The role of curcumin in modulating colonic microbiota during colitis and colon cancer prevention. Inflamm. Bowel Dis. 2015 21 11 2483 2494 10.1097/MIB.0000000000000522 26218141
    [Google Scholar]
  39. Sun X. Pan C. Ying Z. Stabilization of zein nanoparticles with k-carrageenan and tween 80 for encapsulation of curcumin. Int. J. Biol. Macromol. 2020 146 549 559 10.1016/j.ijbiomac.2020.01.053 31917983
    [Google Scholar]
  40. Jithan A.V. Madhavi M. Madhavi K. Preparation and in vitro/in vivo characterization of curcumin microspheres intended to treat colon cancer. J. Pharm. Bioallied Sci. 2012 4 2 164 171 10.4103/0975‑7406.94825 22557928
    [Google Scholar]
  41. Fontes-Candia C. Ström A. Lopez-Sanchez P. López-Rubio A. Martínez-Sanz M. Rheological and structural characterization of carrageenan emulsion gels. Algal Res. 2020 47 101873 10.1016/j.algal.2020.101873
    [Google Scholar]
  42. Cao Y. Khan A. Soltani A. Spectroscopic, density functional theory, cytotoxicity and antioxidant activities of sulfasalazine and naproxen drugs combination. Arab. J. Chem. 2021 14 6 103190 10.1016/j.arabjc.2021.103190
    [Google Scholar]
  43. Jadiya S. Upmanyu N. Sathiyanarayanan A. Jain V. Dubey R. Buwade P. Formulation and development of novel sulfasalazine bilayer tablets for the treatment of arthritis associated with IBD: in-vitro and in-vivo investigations. J. Pharm. Sci. 2024 113 7 1919 1926 10.1016/j.xphs.2024.02.019 38401631
    [Google Scholar]
  44. Mehmood Y. Hammad Y. Umer F. Formulation development using different natural and semi synthetic polymers, in vitro evaluation of colon targeted Sulfasalazine tablets for ulcerative colitis. Int. J. Biosci. 2019 15 1 42 55 10.12692/ijb/15.1.42‑55
    [Google Scholar]
/content/journals/raddf/10.2174/0126673878363141250731125303
Loading
Optimized Formulation of Sulfasalazine and Probiotic-Loaded Carrageenan Microparticles Using Design of Experiments for Effective Colitis Management
Bentham Science Publishers ; https://doi.org/10.2174/0126673878363141250731125303
/content/journals/raddf/10.2174/0126673878363141250731125303
/content/journals/raddf/10.2174/0126673878363141250731125303
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: cellulose acetate phthalate ; sulfasalazine ; carrageenan ; Ulcerative colitis ; inflammatory bowel disease ; Saccharomyces boulardii

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test