Steroid Eluting Esophageal-Targeted Drug Delivery Devices for Treatment of Eosinophilic Esophagitis
Alka Prasher,
Roopali Shrivastava,
Denali Dahl,
Preetika Sharma-Huynh,
Panita Maturavongsadit,
Tiffany Pridgen,
Allison Schorzman,
William Zamboni,
Jisun Ban,
Anthony Blikslager,
Evan S. Dellon,
Soumya Rahima Benhabbour
Affiliations
Alka Prasher
Department of Biomedical Engineering, UNC Chapel Hill & North Carolina State University, Chapel Hill, NC 27599-3290, USA
Roopali Shrivastava
Department of Biomedical Engineering, UNC Chapel Hill & North Carolina State University, Chapel Hill, NC 27599-3290, USA
Denali Dahl
Department of Biomedical Engineering, UNC Chapel Hill & North Carolina State University, Chapel Hill, NC 27599-3290, USA
Preetika Sharma-Huynh
Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA
Panita Maturavongsadit
Department of Biomedical Engineering, UNC Chapel Hill & North Carolina State University, Chapel Hill, NC 27599-3290, USA
Tiffany Pridgen
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA
Allison Schorzman
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-3290, USA
William Zamboni
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-3290, USA
Jisun Ban
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-3290, USA
Anthony Blikslager
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA
Evan S. Dellon
Division of Gastroenterology and Hepatology, UNC School of Medicine, University of North Carolina, Chapel Hill, NC 27599-3290, USA
Soumya Rahima Benhabbour
Department of Biomedical Engineering, UNC Chapel Hill & North Carolina State University, Chapel Hill, NC 27599-3290, USA
Eosinophilic esophagitis (EoE) is a chronic atopic disease that has become increasingly prevalent over the past 20 years. A first-line pharmacologic option is topical/swallowed corticosteroids, but these are adapted from asthma preparations such as fluticasone from an inhaler and yield suboptimal response rates. There are no FDA-approved medications for the treatment of EoE, and esophageal-specific drug formulations are lacking. We report the development of two novel esophageal-specific drug delivery platforms. The first is a fluticasone-eluting string that could be swallowed similar to the string test “entero-test” and used for overnight treatment, allowing for a rapid release along the entire length of esophagus. In vitro drug release studies showed a target release of 1 mg/day of fluticasone. In vivo pharmacokinetic studies were carried out after deploying the string in a porcine model, and our results showed a high local level of fluticasone in esophageal tissue persisting over 1 and 3 days, and a minimal systemic absorption in plasma. The second device is a fluticasone-eluting 3D printed ring for local and sustained release of fluticasone in the esophagus. We designed and fabricated biocompatible fluticasone-loaded rings using a top-down, Digital Light Processing (DLP) Gizmo 3D printer. We explored various strategies of drug loading into 3D printed rings, involving incorporation of drug during the print process (pre-loading) or after printing (post-loading). In vitro drug release studies of fluticasone-loaded rings (pre and post-loaded) showed that fluticasone elutes at a constant rate over a period of one month. Ex vivo pharmacokinetic studies in the porcine model also showed high tissue levels of fluticasone and both rings and strings were successfully deployed into the porcine esophagus in vivo. Given these preliminary proof-of-concept data, these devices now merit study in animal models of disease and ultimately subsequent translation to testing in humans.
