Date on Master's Thesis/Doctoral Dissertation

1-2021

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Matoba, Nobuyuki

Committee Co-Chair (if applicable)

Hamorsky, Krystal

Committee Member

Hamorsky, Krystal

Committee Member

Dryden, Gerald

Committee Member

Feng, Wenke

Committee Member

Siskind, Leah

Committee Member

Yaddanapudi, Kavitha

Abstract

Epicertin (EPT) is a recombinant variant of the cholera toxin B subunit with a C-terminal KDEL endoplasmic retention motif. Previously, orally administered EPT demonstrated mucosal healing activity in acute and chronic dextran sulfate sodium colitis models, indicating its therapeutic potential for ulcerative colitis (UC) treatment. However, oral dosing with EPT requires neutralization of gastric acid prior to administration, hindering its facile application in the treatment of chronic diseases like UC. One solution to this issue is that EPT may also be administered intracolonically without losing efficacy. This work describes the determination of a target intracolonic dose of EPT for future first-in-human safety trials as well as the development of a prototype oral formulation of EPT that prevents stomach acid degradation for pH-dependent release at the colon.

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