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Pharmaceutics
Volume 18
Issue 2
10.3390/pharmaceutics18020248
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Article

Topical Delivery of CNP-miR146a via a Pluronic Lecithin Organogel Enhances Diabetic Wound Healing

by
Bailey D. Lyttle
1,*,
James Bardill
1,
Alyssa E. Vaughn
1,
Anisha Apte
2,
Alyssa San Agustin
2,
Elayaraja Kolanthai
3,
Sudipta Seal
3,
David M. Jackson
4,
Kenneth W. Liechty
2,4 and
Carlos Zgheib
2,4
1
Laboratory for Fetal and Regenerative Biology, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO 80045, USA
2
Laboratory for Fetal and Regenerative Biology, Department of Surgery, Banner Children’s at Diamond Children’s Medical Center, University of Arizona Tucson College of Medicine, Tucson, AZ 85721, USA
3
Advanced Materials Processing and Analysis Center, Nanoscience Technology Center, University of Central Florida, Orlando, FL 32826, USA
4
Ceria Therapeutics, Inc., Tucson, AZ 85721, USA
*
Author to whom correspondence should be addressed.
Pharmaceutics 2026, 18(2), 248; https://doi.org/10.3390/pharmaceutics18020248
Submission received: 30 November 2025 / Revised: 20 December 2025 / Accepted: 25 December 2025 / Published: 17 February 2026
(This article belongs to the Special Issue Nanosystems for Advanced Diagnostics and Therapy)
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Abstract

Background: Diabetes mellitus is common and associated with numerous complications including diabetic foot ulcers (DFU), which affect a third of patients and are associated with high morbidity and mortality. There are limited pharmacologic treatment options available with mixed efficacy. We have developed a novel therapeutic targeting inflammation and oxidative stress by conjugating microRNA-146a to cerium oxide nanoparticles to create CNP-miR146a and have found that injectable CNP-miR146a is associated with improved wound healing in a diabetic murine model. We hypothesized that a topical formulation of CNP-miR146a would be associated with equivalent improvements in wound healing. Methods: Release tests of CNP conjugated to fluorescein isothiocyanate were performed to determine the optimal gel base for sustained release. Diabetic (db/db) mice were cutaneously wounded and treated with topical CNP-miR146a, empty gel, injectable CNP-miR146a, or injectable phosphate-buffered saline (PBS). Wound healing over time was compared between groups. Histological samples were collected and analyzed for CD45 and CD31 positivity at multiple timepoints. Results: CNP-miR146a in a topical pluronic lecithin organogel (PLO) base was associated with significantly improved wound healing compared to empty gel or injected PBS and equivalent to injected CNP-miR146a. Treatment with CNP-miR146a was also associated with decreased CD45 positivity and increased CD31 positivity, suggesting decreased inflammation and improved angiogenesis. Conclusions: Topical delivery of CNP-miR46a in a PLO base holds significant promise as a potential therapeutic for DFU and may improve patient compliance due to ease of delivery.
Keywords: nanomedicine; microRNA; diabetes mellitus; diabetic foot ulcer; oxidative stress; inflammation; angiogenesis nanomedicine; microRNA; diabetes mellitus; diabetic foot ulcer; oxidative stress; inflammation; angiogenesis

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MDPI and ACS Style

Lyttle, B.D.; Bardill, J.; Vaughn, A.E.; Apte, A.; San Agustin, A.; Kolanthai, E.; Seal, S.; Jackson, D.M.; Liechty, K.W.; Zgheib, C. Topical Delivery of CNP-miR146a via a Pluronic Lecithin Organogel Enhances Diabetic Wound Healing. Pharmaceutics 2026, 18, 248. https://doi.org/10.3390/pharmaceutics18020248

AMA Style

Lyttle BD, Bardill J, Vaughn AE, Apte A, San Agustin A, Kolanthai E, Seal S, Jackson DM, Liechty KW, Zgheib C. Topical Delivery of CNP-miR146a via a Pluronic Lecithin Organogel Enhances Diabetic Wound Healing. Pharmaceutics. 2026; 18(2):248. https://doi.org/10.3390/pharmaceutics18020248

Chicago/Turabian Style

Lyttle, Bailey D., James Bardill, Alyssa E. Vaughn, Anisha Apte, Alyssa San Agustin, Elayaraja Kolanthai, Sudipta Seal, David M. Jackson, Kenneth W. Liechty, and Carlos Zgheib. 2026. "Topical Delivery of CNP-miR146a via a Pluronic Lecithin Organogel Enhances Diabetic Wound Healing" Pharmaceutics 18, no. 2: 248. https://doi.org/10.3390/pharmaceutics18020248

APA Style

Lyttle, B. D., Bardill, J., Vaughn, A. E., Apte, A., San Agustin, A., Kolanthai, E., Seal, S., Jackson, D. M., Liechty, K. W., & Zgheib, C. (2026). Topical Delivery of CNP-miR146a via a Pluronic Lecithin Organogel Enhances Diabetic Wound Healing. Pharmaceutics, 18(2), 248. https://doi.org/10.3390/pharmaceutics18020248

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