Drug delivery of zinc to Barrett's metaplasia by oral administration to Barrett's esophagus patients.

Mary C Valenzano, Joanna M Mercado, Xuexuan Wang, E Peter Zurbach, Jonathan Raines, Erin McDonnell, Melissa Morgan, Christopher Farrell, David Rudolph, Austin Hwang, Maura Barr, Dinu Cherian, Robert Bailey, Benjamin Raile, Nicole Albert, James Thornton, Marc Zitin, John Abramson, Gary Newman, Gary Daum, Giancarlo Mercogliano, James M Mullin

Journal: Therapeutic delivery 2014;5(3):257-64

PMID: 24592952

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Abstract

BACKGROUND

Delivery of a pharmacologically effective drug dosage to a target tissue is critical. Barrett's epithelia are a unique challenge for drug delivery of orally administered zinc due to rapid transit down the esophageal lumen, incomplete absorptive differentiation of these epithelia, and the use of proton-pump inhibitor drugs abrogating intestinal uptake of supplemental zinc.

METHODS

Barrett's esophagus patients were administered oral zinc gluconate (26 mg zinc twice daily) for 14 days prior to biopsy procurement. Barrett's biopsies were analyzed for total zinc content by atomic absorption spectroscopy and by western immunoblot for cellular proteins known to be regulated by zinc.

RESULTS

Cellular levels of both the Znt-1 transport protein and the alpha isoform of PKC were over 50% lower in the zinc treatment group.

CONCLUSION

Oral zinc administration can result in effective delivery of zinc to Barrett's epithelia with resulting effects on intracellular signal transduction.

Address: Lankenau Institute for Medical Research, Wynnewood, PA 19096, USA.

DOI: 10.4155/tde.13.151

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MeSH Terms: Administration, Oral, Adult, Aged, Barrett Esophagus, Biopsy, Blotting, Western, Cation Transport Proteins, Dietary Supplements, Drug Delivery Systems, Esophagus, Female, Gluconates, Humans, Male, Metaplasia, Middle Aged, Protein Kinase C-alpha, Signal Transduction, Spectrophotometry, Atomic, Time Factors, Treatment Outcome