Display options
Cite
Aprodu A, Mantaj J, Raimi-Abraham B, et al. Evaluation of a Methylcellulose and Hyaluronic Acid Hydrogel as a Vehicle for Rectal Delivery of Biologics. Pharmaceutics. 2019;11(3)doi: 10.3390/pharmaceutics11030127.
Aprodu, A., Mantaj, J., Raimi-Abraham, B., & Vllasaliu, D. (2019). Evaluation of a Methylcellulose and Hyaluronic Acid Hydrogel as a Vehicle for Rectal Delivery of Biologics. Pharmaceutics, 11(3), . https://doi.org/10.3390/pharmaceutics11030127
Aprodu, Andreea, et al. "Evaluation of a Methylcellulose and Hyaluronic Acid Hydrogel as a Vehicle for Rectal Delivery of Biologics." Pharmaceutics vol. 11,3 (2019). doi: https://doi.org/10.3390/pharmaceutics11030127
Aprodu A, Mantaj J, Raimi-Abraham B, Vllasaliu D. Evaluation of a Methylcellulose and Hyaluronic Acid Hydrogel as a Vehicle for Rectal Delivery of Biologics. Pharmaceutics. 2019 Mar 19;11(3). doi: 10.3390/pharmaceutics11030127. PMID: 30893796; PMCID: PMC6471061.
Copy Download .nbib Format: NLM
Share it on

Pharmaceutics. 2019 Mar 19;11(3). doi: 10.3390/pharmaceutics11030127.

Evaluation of a Methylcellulose and Hyaluronic Acid Hydrogel as a Vehicle for Rectal Delivery of Biologics.

Pharmaceutics

Andreea Aprodu, Julia Mantaj, Bahijja Raimi-Abraham, Driton Vllasaliu

Affiliations

  1. Faculty of Life Sciences & Medicine, School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 9NH, UK. [email protected].
  2. Faculty of Life Sciences & Medicine, School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 9NH, UK. [email protected].
  3. Faculty of Life Sciences & Medicine, School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 9NH, UK. [email protected].
  4. Faculty of Life Sciences & Medicine, School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 9NH, UK. [email protected].

PMID: 30893796 PMCID: PMC6471061 DOI: 10.3390/pharmaceutics11030127

Abstract

Biologics have changed the management of Inflammatory Bowel Disease (IBD), but there are concerns regarding unexpected systemic toxicity and loss of therapeutic response following administration by injection. Local delivery of biologics directly to the inflamed mucosa via rectal enema administration addresses the problems associated with systemic administration. Hydrogels are potentially useful delivery vehicles enabling rectal administration of biologics. Here, we prepared a hydrogel system based on methylcellulose (MC) and hyaluronic acid (HA), which possesses mucosal healing properties, incorporating a model macromolecular drug, namely (fluorescently-labeled) bovine serum albumin (BSA). The BSA-loaded MCHA hydrogel showed temperature-dependent gelation (liquid-like at 20 °C and gel-like at 37 °C) and shear thinning behavior, with these being important and desirable characteristics for rectal application (enabling easy application and retention). BSA release from the MCHA system at 37 °C was linear, with 50% of the loaded drug released within 2 h. The system demonstrated acceptable toxicity towards intestinal (colon) Caco-2 epithelial cells, even at high concentrations. Importantly, application of the BSA-loaded MCHA hydrogel to polarized Caco-2 monolayers, with or without an exemplar absorption enhancer, resulted in transintestinal permeability of BSA. The study therefore indicates that the MCHA hydrogel shows potential for topical (rectal) delivery of biologics in IBD.

Keywords: biologics; biologics delivery; hyaluronic acid; hydrogels; inflammatory bowel disease; intestinal delivery; methylcellulose (MC)

References

  1. Gastroenterology. 1999 Jul;117(1):65-72 - PubMed
  2. Scand J Gastroenterol. 1992 Sep;27(9):721-6 - PubMed
  3. J Pharm Pharmacol. 2004 Sep;56(9):1083-90 - PubMed
  4. Gut. 2007 Jan;56(1):61-72 - PubMed
  5. Gut. 2007 May;56(5):725-32 - PubMed
  6. Tissue Eng Part A. 2009 Mar;15(3):595-604 - PubMed
  7. Mol Pharm. 2009 Jul-Aug;6(4):1083-91 - PubMed
  8. World J Gastroenterol. 2009 Sep 21;15(35):4353-5 - PubMed
  9. Am J Gastroenterol. 2010 Mar;105(3):501-23; quiz 524 - PubMed
  10. PLoS One. 2011;6(5):e19850 - PubMed
  11. J Proteome Res. 2012 Feb 3;11(2):818-28 - PubMed
  12. Drug Dev Ind Pharm. 2013 Apr;39(4):587-92 - PubMed
  13. Eur J Pharm Sci. 2013 Jan 23;48(1-2):104-10 - PubMed
  14. Gut. 1990 Aug;31(8):883-5 - PubMed
  15. Dig Liver Dis. 2013 Dec;45(12):1017-21 - PubMed
  16. J Control Release. 2013 Nov 28;172(1):374-381 - PubMed
  17. Carbohydr Polym. 2014 Nov 4;112:480-5 - PubMed
  18. Gastroenterology. 2015 Jul;149(1):52-55.e2 - PubMed
  19. Sci Transl Med. 2015 Aug 12;7(300):300ra128 - PubMed
  20. BMC Gastroenterol. 2015 Dec 18;15:178 - PubMed
  21. Wounds. 2016 Mar;28(3):78-88 - PubMed
  22. Adv Drug Deliv Rev. 2016 Nov 15;106(Pt B):277-319 - PubMed
  23. Eur J Pharm Biopharm. 2016 Oct;107:88-96 - PubMed
  24. Acta Biomater. 2017 Jan 15;48:247-257 - PubMed
  25. Molecules. 2017 May 30;22(6):null - PubMed
  26. J Tissue Eng. 2017 Sep 06;8:2041731417726464 - PubMed
  27. Eur J Pharm Biopharm. 2018 Mar;124:55-62 - PubMed
  28. Drug Deliv Transl Res. 2019 Apr;9(2):595-614 - PubMed
  29. Carbohydr Polym. 2018 Jun 15;190:248-254 - PubMed
  30. J Inflamm Res. 2018 May 16;11:215-226 - PubMed
  31. Pharm Dev Technol. 2018 Dec;23(10):942-952 - PubMed
  32. Nanomedicine (Lond). 2018 Jun;13(11):1255-1265 - PubMed
  33. Expert Opin Drug Deliv. 2018 Aug;15(8):759-770 - PubMed
  34. Pharmaceutics. 2018 Oct 15;10(4):null - PubMed
  35. J Pharm Sci. 1993 Apr;82(4):392-8 - PubMed

Publication Types

Grant support