Skip to main content
SpringerLink
Log in

Evaluation of Budesonide–Hydroxypropyl-β-Cyclodextrin Inclusion Complex in Thermoreversible Gels for Ulcerative Colitis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

New formulations for topical treatment of ulcerative colitis with budesonide inclusion complex (BUDHP-β-CD) and poloxamers (PL) were developed for future clinical use.

Aims

This study evaluated the efficacy of such novel formulations in a rat model of colitis.

Methods

The PL-BUDHP-β-CD systems were prepared by direct dispersion of the complex (BUD concentration 0.5 mg mL−1) in solutions with PL407 or PL403. Male Wistar rats underwent TNBS-induced colitis and were treated for 5 days by a rectal route, as follows: BUD 1: BUDHP-β-CD + PL407 (18%); BUD 2: BUDHP-β-CD + PL407 (20%); BUD 3: BUDHP-β-CD + PL407 (18%) + PL403 (2%); BUD 4: plain BUD; BUD 5: BUDHP-β-CD; C1: HP-β-CD + PL407 (18%); C2: HP-β-CD + PL407 (20%); C3: HP-β-CD + PL407 (18%) + PL403 (2%); C4: saline. A negative control group without colitis was also used. Colitis was assessed via myeloperoxidase (MPO) activity, and macroscopic and microscopic damage score in colon tissues. Protein levels of TNF-α, IL-1β, IL-10 and endogenous glucocorticoids were obtained using ELISA.

Results

BUDHP-β-CD poloxamer formulations had similar MPO activity when compared with the negative control group. All formulations presented lower MPO activity than BUDHP-β-CD and plain BUD (p < 0.001). BUD 2 produced lower microscopic score values than plain BUD and BUDHP-β-CD (p < 0.01). All formulations with BUDHP-β-CD poloxamers reduced TNF-α levels (p < 0.05).

Conclusion

Novel budesonide inclusion complex formulations improved microscopic damage and reduced colonic MPO activity and TNF-α levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Witaicenis A, Luchini AC, Hiruma-Lima CA, et al. Suppression of TNBS-induced colitis in rats by 4-methylesculetin, a natural coumarin: comparison with prednisolone and sulphasalazine. Chem Biol Interact. 2012;195:76–85.

    Article  CAS  Google Scholar 

  2. Nyuyki KD, Pittman QJ. Toward a better understanding of the central consequences of intestinal inflammation. Ann N Y Acad Sci. 2015;1351:149–154.

    Article  CAS  Google Scholar 

  3. Zeeff SB, Kunne C, Bouma G, de Vries RB, Te Velde AA. Actual usage and quality of experimental colitis models in preclinical efficacy testing: a scoping review. Inflamm Bowel Dis. 2016;22:1296–1305.

    Article  Google Scholar 

  4. Leitner GC, Vogelsang H. Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults. World J Gastrointest Pharmacol Ther. 2016;7:5–20.

    Article  Google Scholar 

  5. Christophi GP, Rengarajan A, Ciorba MA. Rectal budesonide and mesalamine formulations in active ulcerative proctosigmoiditis: efficacy, tolerance, and treatment approach. Clin Exp Gastroenterol. 2016;9:125–130.

    Article  CAS  Google Scholar 

  6. Seibold F, Fournier N, Beglinger C, et al. Topical therapy is underused in patients with ulcerative colitis. J Crohns Colitis. 2014;8:56–63.

    Article  CAS  Google Scholar 

  7. Iborra M, Alvarez-Sotomayor D, Nos P. Long-term safety and efficacy of budesonide in the treatment of ulcerative colitis. Clin Exp Gastroenterol. 2014;7:39–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Lichtenstein GR. Budesonide multi-matrix for the treatment of patients with ulcerative colitis. Dig Dis Sci. 2016;61:9.

    Google Scholar 

  9. Brunner M, Vogelsang H, Greinwald R, et al. Colonic spread and serum pharmacokinetics of budesonide foam in patients with mildly to moderately active ulcerative colitis. Aliment Pharmacol Ther. 2005;22:463–470.

    Article  CAS  Google Scholar 

  10. Lemann M, Galian A, Rutgeerts P, et al. Comparison of budesonide and 5-aminosalicylic acid enemas in active distal ulcerative colitis. Aliment Pharmacol Ther. 1995;9:557–562.

    Article  CAS  Google Scholar 

  11. Hartmann F, Stein J, BudMesa-Study Group. Clinical trial: controlled, open, randomized multicentre study comparing the effects of treatment on quality of life, safety and efficacy of budesonide or mesalazine enemas in active left-sided ulcerative colitis. Aliment Pharmacol Ther. 2010;32:368–376.

    Article  CAS  Google Scholar 

  12. Rashid M, Kaur V, Hallan SS, Sharma S, Mishra N. Microparticles as controlled drug delivery carrier for the treatment of ulcerative colitis: a brief review. Saudi Pharm J. 2016;24:458–472.

    Article  Google Scholar 

  13. Klouda L. Thermoresponsive hydrogels in biomedical applications: a seven-year update. Eur J Pharm Biopharm. 2015;97:338–349.

    Article  CAS  Google Scholar 

  14. Papini JZB, Cereda CMS, Pedrazzoli Júnior J, Alafatti SA, de Araújo DR, Tofoli GR. Pharmacokinetics and pharmacodynamics evaluation of tramadol in thermoreversible gels. Biomed Res Int. 2017;2017:5954629.

    Article  Google Scholar 

  15. Akkari AC, Ramos Campos EV, Keppler AF, et al. Budesonide–hydroxypropyl-β-cyclodextrin inclusion complex in binary poloxamer 407/403 system for ulcerative colitis treatment: a physico-chemical study from micelles to hydrogels. Colloids Surf B Biointerfaces. 2016;138:138–147.

    Article  Google Scholar 

  16. Gotardo ÉM, Ribeiro Gde A, Clemente TR, et al. Hepcidin expression in colon during trinitrobenzene sulfonic acid-induced colitis in rats. World J Gastroenterol. 2014;20:4345–4352.

    Article  Google Scholar 

  17. dos Reis SB, de Oliveira CC, Acedo SC, et al. Attenuation of colitis injury in rats using Garcinia cambogia extract. Phytother Res.. 2009;23:324–329.

    Article  Google Scholar 

  18. Zar JH. Biostatistical Analysis. 5th ed. Prentice Hall: Upper Saddle River; 2010.

    Google Scholar 

  19. Randhawa PK, Singh K, Singh N, Jaggi AS. A review on chemical-induced inflammatory bowel disease models in rodents. Korean J Physiol Pharmacol. 2014;18:279–288.

    Article  CAS  Google Scholar 

  20. Ergang P, Leden P, Bryndová J, et al. Glucocorticoid availability in colonic inflammation of rat. Dig Dis Sci. 2008;53:2160–2167.

    Article  CAS  Google Scholar 

  21. Coccia M, Harrison OJ, Schiering C, et al. IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4(+) Th17 cells. J Exp Med. 2012;209:1595–1609.

    Article  CAS  Google Scholar 

  22. Li L, Liu Z, Yang X, Yan H, Bao S, Fei J. Bioluminescence imaging for IL-1β expression in experimental colitis. J Inflamm (Lond). 2013;10:16.

    Article  Google Scholar 

Download references

Acknowledgments

The authors are grateful to FAPESP (#2014/26200-9) for their financial support.

Author information

Authors and Affiliations

  1. Universidade São Francisco, Av. São Francisco de Assis 218, Bragança Paulista, São Paulo, 12916-900, Brazil

    Carolina Martins Lázaro, Carolina C. de Oliveira & Thalita Rocha

  2. Universidade Estadual de Campinas, Av. Alexandre Cazelatto 999, Paulínia, 13140-000, São Paulo, Brazil

    Alessandra Gambero

  3. Universidade Federal do ABC, Av. dos Estados 5001, Bl A, Torre 3, Lab 503-3, Santo André, São Paulo, 09210-170, Brazil

    Daniele Ribeiro de Araújo

  4. Faculdade São Leopoldo Mandic, Instituto de Pesquisa São Leopoldo Mandic, Rua José Rocha Junqueira 13, Campinas, São Paulo, 13045-75, Brazil

    Cintia Maria Saia Cereda & Giovana Radomille Tofoli

Authors
  1. Carolina Martins Lázaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carolina C. de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessandra Gambero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thalita Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cintia Maria Saia Cereda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniele Ribeiro de Araújo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giovana Radomille Tofoli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovana Radomille Tofoli.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lázaro, C.M., de Oliveira, C.C., Gambero, A. et al. Evaluation of Budesonide–Hydroxypropyl-β-Cyclodextrin Inclusion Complex in Thermoreversible Gels for Ulcerative Colitis. Dig Dis Sci 65, 3297–3304 (2020). https://doi.org/10.1007/s10620-020-06075-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-020-06075-y

Keywords

Search

Navigation