Topical Drug Delivery System as an Anti-Inflammatory and Pro-Angiogenic Therapy for Diabetic Wound Healing

SUMMARY Impaired wound healing in diabetic patients represents a major clinical problem, resulting in prolonged hospitalizations and significant healthcare expenditures. The financial burden of this is extreme, representing $78 billion annually in the U.S. alone. Two-thirds of all non-traumatic amputations are preceded by a diabetic

wound, and every 20 seconds a lower limb is lost to a diabetic wound. The impaired healing of diabetic wounds is multifactorial, but a central pathogenic feature is chronic inflammation. These terrible, infection-prone ulcers are difficult to treat using current technologies and represent a significant under-met need in the marketplace.

Current treatments commonly employed for these conditions involve standard bandages or basic hydrogels which have many drawbacks, including that they cause inflammatory response, need to be removed and changed often, and are not capable of sustained drug release. GelSana Therapeutics, Inc. is addressing this

need with its proprietary wound healing hydrogels that help heal wounds significantly faster and without the downsides of today’s dressings. The hydrogels are based on polymers that repel protein adsorption and prevent the foreign body response. Further, this class of materials have been shown to be anti-inflammatory. In studies

with diabetic mice with impaired wound healing abilities, GelSana has demonstrated that the hydrogels alone cut the healing time down to 2/3 of the time of saline-treated diabetic wounds, matching the healing time of healthy mice. This indicates that the material alone can correct the diabetic impairment to wound healing.

GelSana materials have also been shown to outperform another type of hydrogel used in commercially available products in the time of healing required for these diabetic murine wounds. Furthermore, hydrogels laden with an anti-inflammatory drug cut the healing time down by a staggering one-half. In this project, GelSana proprietary

zwitterionic hydrogels will serve as superior wound dressing materials to aid in correcting the diabetic wound healing impairment by reducing inflammation, where sustained delivery of IL-10 from these dressings will be demonstrated to further resolve chronic inflammation in the diabetic wound environment and improve

vascularization, thus allowing the diabetic ulcer to heal at a rate equivalent to or faster than that found in non- diabetic (healthy) saline-treated wounds. This Phase I project will demonstrate feasibility for GelSana zwitterionic hydrogels with and without IL-10 by (1) characterizing drug release and bioactivity in vitro and (2) assessing

efficacy in an in vivo murine diabetic ulcer model. This will be accomplished with these Aims: Aim 1: To quantify the release rate and bioactivity of IL-10 from zwitterionic hydrogels. Aim 2: To quantify the impact of sustained release of the drug on the ability of the drug-device product to improve wound healing in a

murine model. This work will result in a new class of anti-inflammatory pro-regenerative hydrogel wound dressings with sustained release of novel therapeutics that combat oxidative stress and inflammation and promote angiogenesis in diabetic wounds to therapeutically decrease inflammation, decrease healing time, and

increase tissue repair quality.