P13 - pH-Responsive Microgel System for Targeted NAC Release in Chronic Wound Environments

Saturday, October 11, 2025

10:00 AM - 11:00 AM PDT

Location: Exhibit Hall F, G & H

Presenting Author(s)

CD

Cate DeVane

Undergraduate Student
North Carolina State University, University of North Carolina at Chapel Hill, United States

Co-Author(s)

NZ

Nooshin Zandi, PhD

Postdoctoral Researcher
North Carolina State University
Raleigh, North Carolina, United States

Last Author(s)

Ashley C. Brown

Lampe Distinguished Professor
North Carolina State University and University of North Carolina at Chapel Hill
Raleigh, North Carolina, United States

Primary Investigator(s)

Ashley C. Brown

Lampe Distinguished Professor
North Carolina State University and University of North Carolina at Chapel Hill
Raleigh, North Carolina, United States

Introduction: : Chronic, non-healing wounds present a significant global health burden, impacting over 8 million individuals in the United States alone as of 2020. These wounds, often stemming from underlying conditions such as diabetes, vascular disorders, or autoimmune diseases, are characterized by disruptions in the tightly regulated phases of wound healing. To address these issues, advanced biomaterial-based strategies are gaining traction for their ability to modulate the wound microenvironment and promote tissue repair. Among these, ultra-low crosslinking nanogels (ULCs) have emerged as a promising tool for responsive drug delivery and regenerative support. ULCs, synthesized from poly(acrylic acid) and poly(N-isopropyl acrylamide), exhibit unique responsiveness to pH–a critical parameter altered in chronic wounds. These physiochemical changes, such as more acidic pH and elevated local temperature, can be harnessed to trigger controlled drug release in situ. We have encapsulated N-acetyl-L-cysteine (NAC), a potent antioxidant, anti-inflammatory, and biofilm-disrupting agent, into ULCs to exploit their responsive behavior. The ability of NAC to attenuate oxidative stress and inflammation makes it particularly beneficial for resolving the prolonged inflammatory phase characteristic of chronic wounds, like diabetic ulcers. In future studies, NAC-ULCs will be further integrated into a dual-functional, porous scaffold composed of fibrin-based nanoparticles and Strataprene® (FBN/STR). The FBN component creates a bioactive matrix that supports cellular infiltration and tissue regeneration, while the STR scaffold provides structural integrity and porosity for nutrient exchange and cell migration. The composite platform not only mechanically supports the wound site, but delivers therapeutics in a dynamic, environment-responsive manner.

Materials and

Methods: : ULCs nanogels (90:10 and 80:20 pNIPAm: AAc) were produced by dissolving pNIPAm in water, filtering, and heating solutions to ~70°C under nitrogen. AAc was added, followed by initiation with ammonium persulfate. The reaction proceeded under nitrogen for 6 hours, the product was then filtered, dialyzed for 48-72 hours, and lyophilized to obtain dry ULCs.
NAC was dissolved at 0.05 mg/mL in 1x phosphate buffer saline. For each NAC solution prepared, two parallel formulations were made at pH levels of 6.5 and 8.5. ULCs were added at a final concentration of 10 mg/mL. FBN was also incorporated at a final concentration of 5 mg/mL. The mixtures were gently agitated using a vibration shaker to ensure homogenous dispersion and promote interaction with NAC. After mixing, solutions were allowed to rest at room temperature to ensure complete dissolution and equilibration prior to further analysis.
To assess environmental responsiveness, drug-release profiles were analyzed in both acidic (pH ~6.5), neutral (pH ~7.4), and basic (pH ~8.5) buffer solutions, and at 37℃ and room temperature, simulating chronic wound and physiological conditions, respectively. Cumulative NAC release over time was measured using Ellman’s reagent (DTNB). Colorimetric signal assays were performed using a plate reader to quantify NAC release from ULCs and confirm the system’s drug delivery capability.

Results, Conclusions, and Discussions:: Preliminary results indicate superior NAC release in formulations containing FBN and 90:10 NIPAm: AAc ULCs in acidic conditions after one week (231 μg/mL). Overall, incorporating FBN into formulations increased NAC release for both 80:20 and 90:10 NIPAm: AAc ULCs. Within 80:20 NIPAm: AAc ULC samples, neutral/basic conditions demonstrated greater cumulative NAC release compared to acidic conditions. In 90:10 NIPAm: AAc ULCs, lower pH was associated with heightened release rates in FBN-containing samples. However, on-going studies suggest that this behavior was not replicated in parallel formulations fabricated without FBN. Future studies will provide insight into the ability of smart, dual-responsive drug delivery platforms to modulate the wound microenvironment and promote healing in chronic wounds.

Acknowledgements and/or References (Optional): :