# Development and characterization of ultra-stable insulin analogs for novel therapeutic use

> **NIH NIH F30** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $34,662

## Abstract

Diabetes mellitus poses a major public-health burden. Both in the United States and throughout the world,
progressive increases have been observed in the prevalence of both Type 1 diabetes mellitus (T1DM) and
Type 2 diabetes (T2DM). This application focuses on the development of thermodynamically stable insulin
analogs that may be applied to novel drug-delivery systems. The applicant is an MSTP student who seeks
training in biochemistry toward a future career that integrates clinical care with the development of novel
therapeutics and devices.
Clinical insulin regimens must compensate for the loss of regulated secretion by careful dosing coordinated
with the patient's food intake, level of activity, and results of serial glucose monitoring. Adherence to such
regimens requires self-injections several times a day. Such delivery methods not only cause discomfort for the
patient, but they are also difficult to maintain in terms of timing and accurate administration of doses. The
safety and efficacy of current regimens may be enhanced through the development of alternative mechanisms
for insulin administration. Insulin's nature as a peptide hormone that is susceptible to chemical and
temperature-induced degradation is a major barrier for its implementation in novel delivery systems.
This application describes the combination of two previously characterized stabilizing modifications of the
insulin hormone that will be used to create heat-stable insulin analogs that can be fabricated into PLGA-
polymeric matrices and retain their biological activity. These insulin-infused polymers will be developed into
microneedle implants that will serve as basal insulin delivery systems. These implants will reduce the
frequency of self-injection while delivering safe, consistent, and continuous doses of insulin.
Because of the interdisciplinary nature of the proposed studies, laboratory mentorship by the primary Thesis
Advisor (M. Weiss, M.D., Ph.D.; Professor of Biochemistry, Biomedical Engineering & Medicine) will be
complemented by a master clinician (diabetologist F. Ismail-Beigi, Professor of Medicine), an X-ray
crystallography expert (V. Yee; Associate Professor of Biochemistry), and materials-scientist specializing in
macromolecular sciences (J. Pokorski; Professor of Macromolecular Sciences). Additionally, consulting
advisors D. Anderson and R. Langer, protein engineers at the Massachusetts Institute of Technology, will
provide additional guidance on the development of the project.

## Key facts

- **NIH application ID:** 9832657
- **Project number:** 5F30DK112644-04
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Nischay Kiran Rege
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,662
- **Award type:** 5
- **Project period:** 2016-12-01 → 2020-05-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832657

## Citation

> US National Institutes of Health, RePORTER application 9832657, Development and characterization of ultra-stable insulin analogs for novel therapeutic use (5F30DK112644-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9832657. Licensed CC0.

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