Transdermal Phytopharmaceutical Nanohydrogel System Integrating 4-Hydroxyisoleucine and Gymnemic Acid for Diabetic Ulcer Regeneration

Diabetic foot ulcers (DFUs) are serious, full-thickness wounds that commonly occur on the plantar surface of the foot in diabetic patients. They represent a significant complication of diabetes, with a lifetime risk of 19-34% and are a leading cause of non-traumatic lower-extremity amputations, occurring approximately every 20-30 seconds. The prevalence of DFUs is driven by increasing diabetes rates and ageing populations, resulting in a 5-year mortality rate (~50%) that exceeds that of many cancers and high recurrence rates—up to 65% within five years. To enhance healing, a shift towards multidisciplinary specialised care is occurring, incorporating advanced wound care techniques, smart dressings, and AI diagnostics. Improving global outcomes necessitates better screening, patient education, and equitable access to advanced treatments. Current treatments involve a multidisciplinary approach, including surgical debridement, offloading with complete contact casts, strict glycemic control, and infection management using antibiotics such as clindamycin and vancomycin for MRSA. Advanced therapies include platelet-derived growth factors (like becaplermin), hyperbaric oxygen therapy, and negative pressure wound therapy. Contemporary strategies prioritise controlling exudate, maintaining a moist wound environment, and directly delivering active agents to the ulcer site, with specialised dressings and advanced multipurpose hydrogels recognised as the most effective treatment modalities for DFUs.