Experimental topical therapies show potential for diabetic foot ulcers
Experimental topical therapies for diabetic foot ulcers are showing early promise. Studies described probiotic-based treatments, a medieval antimicrobial mixture and a quercetin-loaded hyaluosome gel with anti-inflammatory and wound-healing effects.
Diabetic foot ulcers are among the most severe and debilitating complications of diabetes mellitus, often progressing to limb amputation due to persistent, non-healing lesions. Topical probiotics, a medieval remedy and a quercetin-loaded hyaluosome gel are being studied as new approaches for wounds that remain locked in a chronic nonhealing state and infections that do not always respond to the antibiotics available today.
Ulcers represent one of the most serious and costly complications of diabetes, characterized by a high risk of recurrence and frequent infections that often defy current standard-of-care treatments. Despite advances in surgical debridement, pressure offloading, and infection control, many diabetic wounds remain in a state of self-perpetuating inflammation due to vascular dysfunction, immune dysregulation, and persistent microbial imbalance.
Topical probiotics have emerged as a promising, though still experimental, approach. Specific probiotic strains such as Lactiplantibacillus plantarum and Lacticaseibacillus rhamnosus secrete antimicrobial peptides, organic acids, and hydrogen peroxide that can disrupt established biofilms. Preclinical studies in diabetic models have shown that these therapies can accelerate wound closure by enhancing collagen deposition and stimulating angiogenesis, while preliminary findings suggest that topical application is well-tolerated and can significantly reduce local bacterial load.
Researchers also found that a medieval remedy called Bald’s eyesalve, a mix of garlic, onion, wine and bile salts, can fight bacteria involved in persistent wound infections. In earlier research, the mixture killed antibiotic-resistant bacteria taken from chronic wounds, including in biofilms, and in the latest study it broke down the protective surfaces of bacteria, reduced the toxins they produce, slowed the early steps of biofilm formation and interfered with basic building processes inside the bacteria. In long-term tests, bacteria developed resistance to standard antibiotics but, because the medieval mixture works in many different ways, bacteria struggled to adapt to it.
A separate study evaluated a quercetin-loaded hyaluosome gel for topical drug delivery in diabetic foot ulcer management. The optimized formulation demonstrated an entrapment efficiency of 88.1%, a mean particle size of 122.42 nm, and a zeta potential of −24 mV. The study reported that the gel significantly reduced the expression of pro-inflammatory cytokines including TGF-β, TNF-α, IL-17 and IL-6, lowered MPO activity, increased GST and GSH levels, downregulated ADAMTS-5 and MMP-13, upregulated TIMP-3 and showed significant suppression of NF-κB expression in skin tissue.
The quercetin-loaded hyaluosome gel showed strong therapeutic potential for diabetic foot ulcer treatment, and both in vitro and in vivo results underscored its ability to attenuate inflammation, enhance antioxidant defenses and promote extracellular matrix remodeling. Researchers said there is still a lot to learn before newer approaches such as the medieval mixture can be explored for safety and effectiveness in people, while topical probiotics remain experimental adjuncts and large-scale, multicenter research is still needed before they can move from the laboratory to clinical use.