# Small Intestine Targeted Fast Acting Oral Insulin Formulation

> **NIH NIH R41** · 5M BIOMED, LLC · 2021 · $299,931

## Abstract

PROJECT SUMMARY
 Diabetes mellitus is a class of metabolic diseases characterized by chronic hyperglycemia due to
impaired insulin secretion and/or insulin resistance. Patients are subject to life-long management of their
diabetic conditions and the high risk of macro and microvascular complications. Insulin therapy is the most
effective means of lowering blood glucose for type 1 diabetes mellitus (T1DM) patients with complete absence
of endogenous insulin and type 2 diabetes mellitus (T2DM) patients with progressively depleted insulin
secreting pancreatic β-cells and insulin resistant organs and tissue. It is also used for controlling short-term
hyperglycemia in gestational diabetes mellitus (GDM). The current therapy is subcutaneous injection or
infusion of insulin. However, the poor patient adherence due to inconvenience and psychological insulin
resistance (PIR) to routine injection is still a major hindrance in managing diabetic patients. Furthermore, long-
term use of insulin injection can cause side effects, including lipodystrophy, iatrogenic hyperinsulinemia, and
hypoglycemia. Orally delivered insulin, on the other hand, possesses advantages in patient adherence and
therapeutic effect by mimicking the physiological path of endogenous insulin. However, the development of
oral insulin formulations has not yet been successful due to low insulin bioavailability, stemming from the
degradation in the highly acidic and protease-active stomach and insufficient permeability through the intestinal
epithelium and mucosa. This STTR Phase I project aims to develop a fast-acting oral insulin formulation based
on the patented innovation of milk protein casein coated drug-carrying nanoparticles (casNP) to encapsulate
insulin and the intestinal absorption enhancer, sodium caprate (C10), for small intestine-targeted delivery of
insulin by protecting insulin and C10 from the gastric pH and protease action but enabling the enzyme-triggered
release of insulin and C10 in the small intestine. The liquid formulation of nano-sized casNP/inslulin/C10 also
facilitates rapid gastric emptying and intestinal permeation and absorption as expected in a fast-acting oral
insulin agent for controlling the postprandial blood glucose levels. Developed casNP/insulin/C10 nanoconstruct
and encapsulated insulin will be labeled with near infrared (NIR) fluorescent dyes for non-invasive tracking of
casNP/insulin/C10 delivery and the subsequent insulin release and absorption in the streptozotocin (STZ)
induced diabetic mouse model. We will prepare and optimize the casNP/insulin/C10 formulation with desired
physiochemical and biological properties, including insulin and C10 loading capacities, stability in the simulated
gastric condition and controlled release in the intestine-mimicking condition (Aim 1). We will determine the
biodistribution of casNP/insulin/C10, plasma and hepatic insulin bioavailability and the systemic cytotoxicity in
STZ-induced diabetic mice using NIR and mag...

## Key facts

- **NIH application ID:** 10385154
- **Project number:** 1R41DK131761-01
- **Recipient organization:** 5M BIOMED, LLC
- **Principal Investigator:** Yuancheng Li
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $299,931
- **Award type:** 1
- **Project period:** 2021-09-20 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10385154

## Citation

> US National Institutes of Health, RePORTER application 10385154, Small Intestine Targeted Fast Acting Oral Insulin Formulation (1R41DK131761-01). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10385154. Licensed CC0.

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