Products Cited in Publications Worldwide Localized delivery of corticosteroids via in situ modification of gut commensals using a synthetic stem peptide prodrug

Localized delivery of corticosteroids via in situ modification of gut commensals using a synthetic stem peptide prodrug

Baryakova, Tsvetelina; Yu, Marina; Segatori, Laura; McHugh, Kevin

DOI:

Abstract

Oral colonic drug delivery systems (CDDSs) are oftentimes associated with a short duration of action and poor tissue specificity. To address these challenges, we engineered an oral prodrug that leverages the engraftment and semi-permanence of gut commensals to create a long-acting colonic drug depot. We show that two synthetic stem peptide probes can be stereoselectively incorporated onto the surface of gut bacteria in C57BL/6 mice following oral administration. We then show that a prodrug consisting of budesonide, a corticosteroid with otherwise limiting side effects used to treat ulcerative colitis (UC), conjugated to one of these probes via a hydrolyzable ester is significantly less bioactive and is cleaved over a period of days to weeks in simulated physiological fluids. This prodrug can be integrated into the bacterial peptidoglycan in vitro and be cleaved into free budesonide over time, thereby improving drug localization and potentially rendering it safer for longer-term use.

Keywords

Bacteria ; peptidoglycan ; colonic drug delivery systems ; corticosteroids ; immunomodulation

Purchased from AmBeed

CY5

A1455193146368-11-895%

CY5

58.0/5mg

Detail
Bis-PEG2-acid

A74292119364-66-095%

Bis-PEG2-acid

83.0/1g

Detail