Hyaluronic acid-functionalized thermoresponsive in situ gel embedded with levofloxacin-loaded PLGA nanoparticles for enhanced diabetic wound healing
Abstract
Diabetic ulcers are a leading cause of lower-extremity amputations, with wound infection being the chief cause of therapeutic failure. Traditional topical dressings fail to maintain effective antibiotic concentrations at the wound site over prolonged periods and cannot eliminate biofilm-embedded organisms. A thermoresponsive injectable in situ gel containing levofloxacin hemihydrate-loaded poly(lactic-co-glycolic acid) nanoparticles, with or without hyaluronic acid, was developed for the local treatment of infected diabetic ulcers. The optimized nanoparticles had a size of 77.1 nm, a zeta potential of +55.90 mV, a polydispersity index of 0.240, and an encapsulation efficiency of 98.6%. The incorporated gels exhibited a sol–gel transition at 32.1–34.6 °C, with suitable viscosity and syringeability, and released levofloxacin for 240 h in formulas A and A + and for 336 h in formula B, in accordance with the Korsmeyer–Peppas model. All formulations exhibited strong in vitro antibacterial activity. However, the thermoresponsive gel functionalized with hyaluronic acid (Formula A + ) produced the greatest therapeutic effect in diabetic mice, significantly improving wound closure, accompanied by augmented tissue regeneration, complete re-epithelialization, and dermal remodeling, with reduced inflammatory cell infiltration and scarring. These results indicate that this system can provide sustained local antibiotic delivery and promote the healing of infected diabetic ulcers.
Read the paper
Related studies
- Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
- Photochemical behavior of levofloxacin
- Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose/ Fluid Volume Ratio
- Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides
- Synthesis of [11C]levofloxacin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.