Chitosan Hydrogels Cross-Linked with Trimesic Acid for the Delivery of 5-Fluorouracil in Cancer Therapy.

Sravani Emani, Anil Vangala, Federico Buonocore, Niousha Yarandi, Gianpiero Calabrese
Author Information
  1. Sravani Emani: School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston-upon-Thames KTI 2EE, UK. ORCID
  2. Anil Vangala: School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston-upon-Thames KTI 2EE, UK.
  3. Federico Buonocore: School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston-upon-Thames KTI 2EE, UK.
  4. Niousha Yarandi: School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston-upon-Thames KTI 2EE, UK.
  5. Gianpiero Calabrese: School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston-upon-Thames KTI 2EE, UK. ORCID

Abstract

Chitosan exhibits unique properties making it a suitable material for drug delivery. Considering the rising popularity of hydrogels in this field, this work offers a comprehensive study of hydrogels constituted by chitosan and cross-linked with 1,3,5-benzene tricarboxylic acid (BTC; also known as trimesic acid). Hydrogels were prepared by cross-linking chitosan with BTC in different concentrations. The nature of the gels was studied through oscillatory amplitude strain and frequency sweep tests within the linear viscoelastic region (LVE) limit. The flow curves of the gels revealed shear thinning behavior. High G' values imply strong cross-linking with improved stability. The rheological tests revealed that the strength of the hydrogel network increased with the cross-linking degree. Hardness, cohesiveness, adhesiveness, compressibility, and elasticity of the gels were determined using a texture analyzer. The scanning electron microscopy (SEM) data of the cross-linked hydrogels showed distinctive pores with a pore size increasing according to increasing concentrations (pore size range between 3-18 µm). Computational analysis was performed by docking simulations between chitosan and BTC. Drug release studies employing 5-fluorouracil (5-FU) yielded a more sustained release profile with 35 to 50% release among the formulations studied in a 3 h period. Overall, this work demonstrated that the presence of BTC as cross-linker leads to satisfactory mechanical properties of the chitosan hydrogel, suggesting potential applications in the sustained release of cancer therapeutics.

Keywords

References

  1. Adv Drug Deliv Rev. 2013 Aug;65(9):1188-203 [PMID: 23631979]
  2. Arch Pharm Res. 2013 Jan;36(1):94-101 [PMID: 23371803]
  3. J Comput Chem. 2004 Oct;25(13):1605-12 [PMID: 15264254]
  4. Colloids Surf B Biointerfaces. 2014 Jan 1;113:346-51 [PMID: 24126319]
  5. J Pharm Pharmacol. 2005 Oct;57(10):1251-59 [PMID: 16259753]
  6. Int J Nanomedicine. 2011;6:2143-53 [PMID: 22114478]
  7. AAPS PharmSciTech. 2018 May;19(4):1520-1528 [PMID: 29464592]
  8. Carbohydr Res. 1991 Apr 2;211(1):17-23 [PMID: 1773428]
  9. J Artif Organs. 2006;9(1):8-16 [PMID: 16614797]
  10. Polymers (Basel). 2021 Sep 24;13(19): [PMID: 34641071]
  11. Nanomedicine. 2009 Sep;5(3):323-33 [PMID: 19523427]
  12. Acta Biomater. 2012 Jul;8(7):2688-96 [PMID: 22487929]
  13. Int J Biol Macromol. 1996 Apr;18(3):237-42 [PMID: 8729036]
  14. J Colloid Interface Sci. 2002 May 15;249(2):316-21 [PMID: 16290603]
  15. Carbohydr Polym. 2016 Jun 25;144:245-53 [PMID: 27083815]
  16. J Phys Chem B. 2016 Jul 7;120(26):5916-26 [PMID: 26958864]
  17. Soft Matter. 2016 Nov 4;12(43):8861-8868 [PMID: 27734051]
  18. Pharmaceuticals (Basel). 2021 Jun 11;14(6): [PMID: 34207951]
  19. J Pharm Pharmacol. 2018 Nov;70(11):1494-1502 [PMID: 30182425]
  20. Mar Drugs. 2019 Jun 25;17(6): [PMID: 31242678]
  21. World J Gastroenterol. 2008 Jun 14;14(22):3554-62 [PMID: 18567086]
  22. Int J Nanomedicine. 2021 Dec 16;16:8141-8158 [PMID: 34949922]
  23. J Biol Eng. 2020 Aug 3;14:22 [PMID: 32774454]
  24. Biomacromolecules. 2005 Mar-Apr;6(2):653-62 [PMID: 15762626]
  25. Adv Drug Deliv Rev. 2013 Aug;65(9):1234-70 [PMID: 23872012]
  26. Materialia (Oxf). 2021 Mar;15: [PMID: 33367226]
  27. Curr Drug Deliv. 2006 Oct;3(4):351-8 [PMID: 17076636]
  28. Carbohydr Polym. 2018 Nov 1;199:445-460 [PMID: 30143150]
  29. Mater Sci Eng C Mater Biol Appl. 2020 May;110:110609 [PMID: 32204060]
  30. Int J Biol Macromol. 2019 May 15;129:827-843 [PMID: 30708011]
  31. Int J Biol Macromol. 2017 Nov;104(Pt A):1254-1266 [PMID: 28655661]
  32. Int J Pharm. 2016 Jan 30;497(1-2):210-21 [PMID: 26608619]
  33. Int J Biol Macromol. 1999 Nov;26(2-3):119-28 [PMID: 10517518]
  34. Soft Matter. 2012;8(12):3280-3294 [PMID: 22419946]
  35. Food Funct. 2017 Oct 18;8(10):3647-3653 [PMID: 28914313]
  36. Int J Biol Macromol. 2019 Mar 15;125:979-988 [PMID: 30572059]
  37. Int J Pharm. 2017 May 25;523(2):545-555 [PMID: 28449923]
  38. Sci Rep. 2017 Mar 03;7:42717 [PMID: 28256516]
  39. Drug Deliv. 2008 Jan;15(1):57-67 [PMID: 18197525]
  40. Molecules. 2019 Feb 08;24(3): [PMID: 30744011]
  41. J Control Release. 2007 Jun 22;119(3):313-9 [PMID: 17490772]
  42. J Comput Chem. 2010 Jan 30;31(2):455-61 [PMID: 19499576]
  43. Theor Biol Med Model. 2013 Oct 24;10:63 [PMID: 24156411]
  44. J Biomed Mater Res B Appl Biomater. 2014 Jul;102(5):1063-73 [PMID: 24357498]
  45. J Pharm Biomed Anal. 2003 Aug 21;32(6):1149-58 [PMID: 12907258]
  46. J Funct Biomater. 2018 Jan 24;9(1): [PMID: 29364833]
  47. Int J Biol Macromol. 2019 Jan;121:104-112 [PMID: 30291928]
  48. Expert Opin Drug Deliv. 2014 Jun;11(6):901-15 [PMID: 24848309]
  49. Nanomaterials (Basel). 2020 Sep 24;10(10): [PMID: 32987697]
  50. J Adv Res. 2015 Mar;6(2):105-21 [PMID: 25750745]
  51. RSC Adv. 2019 Oct 1;9(53):31078-31091 [PMID: 35529386]
  52. Adv Drug Deliv Rev. 2001 Dec 31;53(3):321-39 [PMID: 11744175]
  53. Mater Sci Eng C Mater Biol Appl. 2021 Sep;128:112340 [PMID: 34474890]
  54. Int J Adv Res (Indore). 2016 Mar;4(3):411-427 [PMID: 27819009]