A Thermosensitive and Biodegradable Hydrogel as a Delivery System for the Local and Controlled Release of a Blood Pressure Drug (Valsartan) Combined with Senolytics (Dasatinib and Quercetin) to Treat Chronic Diabetic Wounds

JHU Ref #: C16199

Value Proposition:

1. Provides a slow, sustained release of a combination therapy to reverse cellular senescence and enhance collagen production in proliferating and senescent primary dermal fibroblasts.
2. Utilizes a thermosensitive and biodegradable hydrogel for sustained release of nanoparticles and drugs.
3. Requires fewer applications compared to traditional treatments.
4. Potential applications in various therapeutic areas beyond chronic wound management, including general collagen production and partial reversal of cellular senescence.

Unmet Need:

Conditions requiring reversal of cellular senescence and enhanced collagen production, such as aging skin and wound healing, present significant management challenges. These issues often involve impaired healing and increased risk of complications. Chronic wounds, including those associated with diabetes, also suffer from factors like impaired blood flow and infection risk, leading to non-healing ulcers and severe complications. Current treatments frequently fall short in addressing the complex pathophysiology of these conditions, resulting in persistent infections, extended hospitalizations, and reduced quality of life. There is a critical need for innovative solutions that target cellular senescence and enhance collagen production in proliferating and senescent cells.

Technology Description:

Researchers at Johns Hopkins have developed a hydrogel-based formulation designed for sustained release of different therapeutic agents as free drugs or loaded in targeted nanoparticles, used to treat the accumulation of senescent dermal fibroblasts and increase the production of collagen by both proliferating and senescent cells. The technology offers sustained therapeutic effects, making it particularly effective for chronic diabetic wounds, and applicable to a range of conditions requiring reversal of cellular senescence and enhanced collagen production.

Stage of Development:

1. Thermosensitive hydrogel-nanoparticle system fully characterized with in vitro studies.

Data Availability: Publications containing data listed below

Inventors:

1. Efrosini Kokkoli
2. Peter Abadir
3. Jeremy Walston
4. Paul Kuhn

Patent Status: Provisional patent application filed

Publication(s):

1. Kuhn, P.M., Chen, S., Venkatraman, A., Abadir, P.M., Walston, J.D., and Kokkoli, E. (2024). Co-Delivery of Valsartan and Metformin from a Thermosensitive Hydrogel-Nanoparticle System Promotes Collagen Production in Proliferating and Senescent Primary Human Dermal Fibroblasts. Biomacromolecules, DOI: 10.1021/acs.biomac.3c01461.
2. Abadir, P., Hosseini, S., Faghih, M., Ansari, A., Lay, F., Smith, B., Beselman, A., Vuong, D., Berger, A., Tian, J., Rini, D., Keenahan, K., Budman, J., Inagami, T., Fedarko, N., Marti, G., Harmon, J., & Walston, J. (2018). Topical Reformulation of Valsartan for Treatment of Chronic Diabetic Wounds. The Journal of investigative dermatology, 138(2), 434–443.
3. Vidyasagar, A., Ku, S. H., Kim, M., Kim, M., Lee, H. S., Pearce, T. R., McCormick, A. V., Bates, F. S., & Kokkoli, E. (2017). Design and Characterization of a PVLA-PEG-PVLA Thermosensitive and Biodegradable Hydrogel. ACS macro letters, 6(10), 1134–1139.