James Elwell

Pronouns

He/Him/His, They/Them/Theirs

Job Title

Research Trainee

Academic Rank

Department

Anesthesiology, Perioperative and Pain Medicine

Authors

James Elwell, Yuhan Lee, Tammy Lo, Chung-Yi Tseng, Yangshuo Hu, Margery A Connelly, Christos S Mantzoros, Jeffrey Karp, and Ali Tavakkoli

Principal Investigator

Yuhan Lee

Research Category: Cardiovascular, Diabetes, and Metabolic Disorders

Luminal Coating of the Intestine for Oral Peptide Delivery

Scientific Abstract

Oral delivery is a patient-preferred route of drug administration. However, delivering protein therapeutics to the intestinal mucosa of the gastrointestinal tract remains a challenge due to obstacles within the small bowel such as low pH, high gastric intensity, and proteolytic enzymes. Here we developed an orally administered gut-coating formulation to protect protein drug cargo from harsh gastrointestinal conditions and to target delivery to the intestinal mucosa. By screening biomaterials, we identified a top performing formulation using sucrose octasulfate aluminum complex to develop a pH independent complex coacervate formulation, that acts as a luminal coating of the intestines (LuCI). LuCI improves oral drug delivery to the small bowel mucosa by protecting protein therapeutics from gastric acid exposure and degradation. We use horseradish peroxidase (HRP) as a model drug to demonstrate LuCI maintains protein activity before and after exposure to simulated gastric fluid (pH=1), while naked HRP experienced complete loss of activity in the formulation. We engineered the LuCI formulation to gradually release HRP with 62% of cargo released after four hours, and another 10% released after 24 hours. Our LuCI formulation provides the potential to improve the efficacy of oral drug delivery through protection of protein drugs from the gastric environment.

Lay Abstract

Oral drug delivery is a patient-preferred method of administration of medication. However, many medications exist as proteins and lack the ability to enter through the small bowel due to a variety of obstacles such as an acidic intestinal environment and digestive fluids that breakdown the proteins before they can take effect. Here we developed an orally administered gut-coating formulation that can protect these protein drugs from the intestinal barriers and increase the amount of protein that can enter through the small bowel. We identified a paste-like formulation that can coat the intestinal wall and protect protein drugs from degradation and stomach acid exposure. We delivered a model drug in the gut-coating material to measure release speed of a protein drug from it. Our gut-coating material also protects the model drug from exposure to stomach acid. This gut-coating material has potential to improve the delivery protein drugs through oral administration.

Clinical Implications

Our LuCI formulation provides the potential to improve the efficacy of oral drug delivery through protection of protein drugs from the gastric environment. This provides the ability to improve delivery formats for treatments such as insulin.

Luminal Coating of the Intestine for Oral Peptide Delivery

Scientific Abstract

Lay Abstract

Clinical Implications

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