Spray-Dried Formulation of Epicertin, a Recombinant Cholera Toxin B Subunit Variant That Induces Mucosal Healing.

Autor: Reeves MA; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA., Royal JM; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA.; James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA., Morris DA; James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.; Center for Predictive Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA., Jurkiewicz JM; James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA., Matoba N; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA.; James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.; Center for Predictive Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA., Hamorsky KT; James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.; Center for Predictive Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.; Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2021 Apr 18; Vol. 13 (4). Date of Electronic Publication: 2021 Apr 18.
DOI: 10.3390/pharmaceutics13040576
Abstrakt: Epicertin (EPT) is a recombinant variant of the cholera toxin B subunit, modified with a C-terminal KDEL endoplasmic reticulum retention motif. EPT has therapeutic potential for ulcerative colitis treatment. Previously, orally administered EPT demonstrated colon epithelial repair activity in dextran sodium sulfate (DSS)-induced acute and chronic colitis in mice. However, the oral dosing requires cumbersome pretreatment with sodium bicarbonate to conserve the acid-labile drug substance while transit through the stomach, hampering its facile application in chronic disease treatment. Here, we developed a solid oral formulation of EPT that circumvents degradation in gastric acid. EPT was spray-dried and packed into enteric-coated capsules to allow for pH-dependent release in the colon. A GM1-capture KDEL-detection ELISA and size-exclusion HPLC indicated that EPT powder maintains activity and structural stability for up to 9 months. Capsule disintegration tests showed that EPT remained encapsulated at pH 1 but was released over 180 min at pH 6.8, the approximate pH of the proximal colon. An acute DSS colitis study confirmed the therapeutic efficacy of encapsulated EPT in C57BL/6 mice upon oral administration without gastric acid neutralization pretreatment compared to vehicle-treated mice ( p < 0.05). These results provide a foundation for an enteric-coated oral formulation of spray-dried EPT.
Databáze: MEDLINE
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