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Publication Date

5-2022

Abstract

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease affecting children at an increasing rate leading to poor weight gain, vomiting, esophageal strictures and increased health care burden from repeated endoscopies. Oral budesonide is the only drug commercially available for treatment, but adverse effects and compliance limit its utility.

We seek to design a microscale, low-aspect ratio, biodegradable, dispersible form of budesonide with controlled release. Our first step is to fabricate thin films utilizing common mucoadhesive polymers (chitosan and sodium alginate) embedded with budesonide. Here we report on the release characteristics of these thin films.

METHODS: Budesonide is suspended in 5% w/v sodium alginate (NaAlg) in water. Using a spin coating method, we first deposit a thin film of 0.25% chitosan to improve wettability. We then deposit a thin film of budesonide/NaAlg solution on silicon wafers. Finally, calcium chloride (CaCl2) solutions of 50 mM, 100 mM, and 400 mM are deposited in the same manner to allow for NaAlg crosslinking. The final film is approximately 1.5-2 µm thick measured with profilometer. The chitosan contributes negligible thickness and the CaCl2 step does not change the thickness of the NaAlg layer. After spin coating the film, we measured a 3cm x 3cm square of the film and removed it from the wafer using a razor blade. The square was placed in 5 mL of artificial saliva at 37°C and 1 mL samples were removed at time points 1 min, 10 min, 20 min, 30 min, and 40 minutes. One mL of fresh saliva was replaced to keep the volume at 5 mL. Budesonide concentration in the samples was measured using UV high performance liquid chromatography (HPLC).

RESULTS:

All concentrations of CaCl2 resulted in a thin film that was easily handled and pliable (Figure 1). All three crosslinked films maintained the majority of their structural integrity for the duration of the drug release study. Significant breakdown of the films was not seen until around 1 hour in saliva. The lower concentration of CaCl2 for crosslinking resulted in faster release of the budesonide into the surrounding saliva (Figure 2). However, all concentrations show a steady, controlled release profile.

CONCLUSIONS:

We have successfully fabricated budesonide embedded NaAlg thin films with controlled release characteristics. Our next steps to make microscale thin films (microdiscs) and evaluate how the low aspect ratio and mucoadhesive properties affect esopahgeal retention.

Document Type

Poster

Budesonide Embedded Sodium Alginate Thin Films For Controlled Release To The Esophagus

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