Products Cited in Publications Worldwide N-Salicyloyl acidic amino acids are a promising colon-specific promoiety of riluzole against rat colitis

N-Salicyloyl acidic amino acids are a promising colon-specific promoiety of riluzole against rat colitis

Kim, Jaejeong; Kang, Changyu; Jung, Yunjin

DOI:

Abstract

Purpose: In our previous study, (RLZ) azo-linked to (RAS) was prepared as a colon-targeted RLZ prodrug against rat colitis. However, was not a satisfactory colon-targeted prodrug because of its non-negligible systemic absorption, leading to low colonic delivery efficiency and the ability to limit the systemic absorption of RLZ. This study aimed to improve the colon specificity and anticolitic activity of . Methods: (SA) was conjugated with the acidic amino acids (Asp) and (Glu) and subsequently azo-coupled with to yield Asp-conjugated (RAS-Asp) and Glu-conjugated (RAS-Glu). Results: Amino acid-conjugated lowered the distribution coefficient and cell permeability of while exhibiting a release profile of RLZ similar to that of in the cecal contents. Upon oral gavage, amino acid-conjugated delivered a larger amount of RLZ to the cecum than . The ability of amino acid-conjugated to limit the systemic absorption of RLZ was greater than that of . No significant differences were observed in the colon-specific performance between RAS-Asp and RAS-Glu. In a DNBS-induced rat colitis model, amino acid-conjugated was more effective than in ameliorating colonic damage and inflammation and modulating the anti-inflammatory GSK3β-IL-10 pathway in the inflamed colon, without a significant difference between RAS-Asp and RAS-Glu. Conclusion: Conjugation of acidic amino acids with improved the colon specificity, anticolitic activity, and safety of . N-Salicyloyl acidic amino acids may act as high-performance colon-specific promiety for a candidate drug modifiable to a colon-targeted prodrug with an azo bond as a colon-specific link.

Keywords

; Colon-targeted prodrug ; Colitis ; Acidic amino acids ; High performance colon-specific promoiety

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