An Injectable Ibuprofen Sustained-Release Composite Hydrogel System Effectively Accelerates Diabetic Wound Healing via Anti-Inflammatory Effects and Angiogenesis

Apr 16, 2025International journal of nanomedicine

Injectable Ibuprofen Gel Speeds Up Diabetic Wound Healing by Reducing Inflammation and Supporting New Blood Vessel Growth

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Abstract

The optimized system significantly accelerates wound closure within 14 days.

Excessive inflammation in may prolong healing and increase risks of severe complications.
The hydrogel integrates ibuprofen with a composite of oxidized alginate and gelatin to enhance drug delivery.
Physicochemical analyses indicate improved mechanical strength and favorable biocompatibility of the hydrogel.
The system allows for controlled and sustained release of ibuprofen, addressing solubility and absorption issues.
Cellular and animal studies show enhanced tissue regeneration, including increased granulation tissue and collagen deposition.

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PURPOSE: Excessive inflammation in , driven by hyperglycemia, prolongs healing, increases the risk of non-healing ulcers, and can lead to severe complications such as amputation or life-threatening infections. Recurrent wound infections and prolonged treatment impose significant economic and psychological burdens, drastically reducing patients' quality of life. Modulating the inflammatory response is a promising strategy to accelerate diabetic wound healing. Ibuprofen (IBU), a widely used anti-inflammatory and analgesic agent, has the potential to promote healing by mitigating excessive inflammation and alleviating wound-associated pain. However, its clinical application is hindered by poor water solubility and a short half-life. Therefore, a controlled and sustained-release system for IBU could enhance its therapeutic efficacy in diabetic wound management.

MATERIALS AND METHODS: Here, we present an in situ multi-crosslinked composite system that integrates oxidized alginate (OSA), methacryloylated gelatin (GelMA), and an ibuprofen/amino-modified β-cyclodextrin inclusion complex (IBU/CD-NH) via ion crosslinking, photocrosslinking, and Schiff-base reactions. 2

RESULTS: The optimized hydrogel formulation was synthesized at 35°C, with a P/A molar ratio of 2 and an methacrylamide(MA) volume fraction of 20%. Physicochemical and biocompatibility analyses demonstrated that the IBU-loaded composite hydrogel exhibits enhanced mechanical strength, favorable biocompatibility, tunable degradation, and injectability. This system effectively addresses IBU's solubility and absorption challenges while conforming to wounds of varying shapes and sizes, enabling controlled and sustained drug release. Cellular and animal studies confirmed that the hydrogel continuously and uniformly releases IBU, exerting anti-inflammatory effects while promoting angiogenesis and fibroblast migration. This leads to enhanced granulation tissue formation, collagen deposition, and epidermal regeneration, significantly accelerating wound closure within 14 days.

CONCLUSION: By simultaneously suppressing inflammation and stimulating tissue regeneration through controlled IBU release, this hydrogel system offers a highly effective strategy for diabetic wound healing and holds strong potential for clinical application.

Key numbers

98.8%

Wound Healing Rate

Final wound closure rates on day 14 for Gel-IBU group.

82.1%

Collagen Deposition

Collagen levels in the Gel-IBU group on day 14.

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Abstract

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