In vitro digestion and fermentation of 5-formyl-aminosailcylate-inulin: A potential prodrug of 5-aminosalicylic acid

Annette L. Hartzell, María X. Maldonado-Gómez, Junyi Yang, Robert W. Hutkins, Devin J. Rose

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Many carbohydrate polymers that have been used as carriers for colon-targeted drugs have shown benefits against colonic diseases. The objectives of this project were to (1) synthesize a derivative of 5-aminosalicylic acid (5-ASA), a drug used to treat inflammatory bowel disease, containing inulin, a carbohydrate polymer that has shown benefits against inflammatory bowel disease; (2) quantify the release of 5-ASA from the conjugate during in vitro digestion and fermentation; and (3) determine the in vitro fermentation properties of the conjugated inulin. Inulin was esterified with 5-formyl-aminosalicylic acid (5-fASA), a derivative of 5-ASA, with a degree of substitution of 0.185±0.014. During in vitro digestion and fermentation, 56.2±6.5% of 5-fASA was released in 24 h. Gut bacteria did not deformylate 5-fASA to 5-ASA as anticipated. Though conjugation of inulin with 5-fASA reduced bifidogenicity at 24 h compared with native inulin (8.26±0.03 log cfu/g versus 8.59±0.09 log cfu/g, respectively, p<0.01), conjugated 5-fASA-inulin showed protracted fermentation with higher short chain fatty acid (SCFA) and equivalent butyrate concentration at 24 h (9.02±0.68 μmol SCFA/mg carbohydrate versus 7.54±0.53 μmol SCFA/mg carbohydrate, p<0.01; 2.16±0.22 μmol butyrate/mg carbohydrate versus 2.34±0.17 μmol butyrate/mg carbohydrate, respectively, p=0.09). These data suggest that conjugation of inulin with 5-fASA may support SCFA and especially butyrate-producing bacteria through inulin fermentation in the distal colon, an important site of inflammation, together with delivery of 5-fASA. However, gut bacteria were unable to hydrolyze the formyl group from 5-fASA; thus alternative strategies to conjugate 5-ASA to inulin or remove the formyl group from 5-fASA are needed.

Original languageEnglish (US)
Pages (from-to)8-14
Number of pages7
JournalBioactive Carbohydrates and Dietary Fibre
Volume2
Issue number1
DOIs
StatePublished - Nov 4 2013

Fingerprint

Aminosalicylic Acid
Mesalamine
in vitro digestion
Inulin
inulin
Prodrugs
Fermentation
Digestion
fermentation
acids
Volatile Fatty Acids
Butyrates
Carbohydrates
short chain fatty acids
butyrates
carbohydrates
Bacteria
Polymers
inflammatory bowel disease
Derivatives

Keywords

  • 5-aminosalicylic acid
  • Drug delivery
  • Fermentation
  • Inflammatory bowel disease
  • Mesalamine
  • Prebiotic

ASJC Scopus subject areas

  • Food Science
  • Biochemistry
  • Organic Chemistry

Cite this

In vitro digestion and fermentation of 5-formyl-aminosailcylate-inulin : A potential prodrug of 5-aminosalicylic acid. / Hartzell, Annette L.; Maldonado-Gómez, María X.; Yang, Junyi; Hutkins, Robert W.; Rose, Devin J.

In: Bioactive Carbohydrates and Dietary Fibre, Vol. 2, No. 1, 04.11.2013, p. 8-14.

Research output: Contribution to journalArticle

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