Development of ex-vivo and in-vivo models to assess the performance of an oral biotherapeutic delivery system (OBDS) capsule

This preclinical study determined the appropriate animal models to use for future assessment of OBDS device performance and pharmacokinetics.

Oral delivery of biologics, peptides, and nucleic acids has proven difficult due to the harsh conditions of the upper gastrointestinal tract and poor absorption in the small intestinal mucosa. The current state of-the-art technology for a successful oral protein delivery provides around 1% bioavailability when delivered as an oral tablet.1

We aim to develop an oral biotherapeutic delivery system (OBDS) that avoids drug degradation in the upper gastrointestinal tract and increases bioavailability via liquid jet delivery to the small intestine. The OBDS capsule operates autonomously and provides a needleless injection to deposit the liquid drug payload into the submucosal space of the proximal small intestine.

In this preclinical study, our objectives were to:

  1. Evaluate ex-vivo tissue ink deposition in both canine and swine tissue as compared to human tissue to inform animal model selection for further preclinical studies.
  2. Assess the autonomous trigger function of the OBDS capsule in vivo in the canine model.

What did we find?

Assessment of submucosal injection and absorption should be performed in the swine model for human translation of oral bioavailability, because injection volume/deposition is comparable to human.

Results suggest the canine model can be utilized to assess consistency and reproducibility of the OBDS capsule function, and triggers can be modified to adjust small intestinal deployment time.

We have successfully demonstrated ≥ 83% deployment accuracy of autonomous OBDS capsules in the canine small intestine, and consistent deployment time post gastric emptying without early deployment in the stomach.2

Poster presented at Controlled Release Society Annual Meeting, July 13-14, 2022

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REFERENCES

  1. Overgaard RV, Navarria A, Ingwersen SH, Bækdal TA, Kildemoes RJ. Clinical Pharmacokinetics of Oral Semaglutide: Analyses of Data from Clinical Pharmacology Trials. Clin Pharmacokinet. 2021;60(10):1335-1348.
  2. Lee SN, Stork C, Smith J, et al. Development of ex-vivo and in-vivo models to assess the performance of an oral biotherapeutic delivery system (OBDS) capsule. Poster presented at: Controlled Release Society Annual Meeting, July 13-14, 2022, Montreal, Canada.