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Purpose <p>Diabetic wound represent a major clinical challenges due to prolong inflammation, increased microbial burden and delayed healing. The study developed a pH- and temperature-responsive hydrogel composite loaded with Neomycin and Bromelain for sustained drug release, enhanced wound repair, pH-triggered swelling and temperature-induced gelation in the wound microenvironment.</p> Methods <p>The hydrogel was optimized by varying polymer concentrations, including the pH- temperature responsive polymer, carboxymethyl chitosan and Pluronic<sup>®</sup> F-127. Formulations were comprehensively characterized in vitro for visual observation, pH, drug content, permeation flux, viscosity, rheology, texture, and stability. In vivo wound-healing studies were conducted to assess wound closure efficacy and wound exudates were analyzed for hydroxyproline, antioxidant biomarkers, and total protein content.</p> Results <p>The optimized hydrogel composite (FS2) consists of polymers: carboxymethyl chitosan (15&#xa0;mg), Pluronic<sup>®</sup> F-127 (1.5% w/v), hyaluronic acid (0.2% w/v), HPMC (0.4% w/v), and carbopol 940 (1% w/v). SEM revealed a smooth, spherical, swollen, layered surface particle surface, ideal for wound interaction. The drug content ranged 97.3 ± 0.47% to 99.40 ± 0.10%. Ex vivo permeation showed steady-state flux of Neomycin (45.16&#xa0;µg/cm²/h) and bromelain (36.78&#xa0;µg/cm²/h) over 48&#xa0;h from the Neom + Brom−loaded hydrogel. FTIR and XRD confirmed non-interacting drugs in molecular dispersion within the hydrogel composite. The Neom + Brom–loaded hydrogel-treated group showed significantly higher hydroxyproline levels (<i>p</i> &lt; 0.05) on Day 15. This composite achieved greater wound closure efficacy than placebo or plain drug treatments on day 15 (visibly evident). Biochemical analysis of Neom + Brom − loaded hydrogel composite revealed elevated antioxidant biomarkers GPx, SOD, catalase), and reduced MDA levels in excised wound of Wistar rats, while the histopathology confirmed no infiltration of inflammatory cells, and increased collagen deposition versus controls, indicating accelerated wound healing.</p> Conclusion <p>The pH/temperature−responsive hydrogel composite shows promising potential as an effective wound healing therapy combining anti-inflammatory, and anti-oxidant and anti-bacterial properties to enhance tissue regeneration.</p>

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pH- and Temperature-Responsive Hydrogel Composite Dual-Loaded with Neomycin and Bromelain for Enhanced Diabetic Wound Repair

  • 期刊论文

  • 发表日期：

    2026年4月6日

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  • M Yasmin Begum,
  • Anugya Chauhan,
  • Md Habban Akhter,
  • Mona Al hamod,
  • Hamoud Alotaibi,
  • Bjad K. Almutairy,
  • Maha Alsunbul,
  • Md Sajid Ali,
  • Sarfaraz Ahmad,
  • Ibrahim AA Ibrahim,
  • Imran Shahid,
  • Naiyer Shahzad

摘要

Purpose

Diabetic wound represent a major clinical challenges due to prolong inflammation, increased microbial burden and delayed healing. The study developed a pH- and temperature-responsive hydrogel composite loaded with Neomycin and Bromelain for sustained drug release, enhanced wound repair, pH-triggered swelling and temperature-induced gelation in the wound microenvironment.

Methods

The hydrogel was optimized by varying polymer concentrations, including the pH- temperature responsive polymer, carboxymethyl chitosan and Pluronic® F-127. Formulations were comprehensively characterized in vitro for visual observation, pH, drug content, permeation flux, viscosity, rheology, texture, and stability. In vivo wound-healing studies were conducted to assess wound closure efficacy and wound exudates were analyzed for hydroxyproline, antioxidant biomarkers, and total protein content.

Results

The optimized hydrogel composite (FS2) consists of polymers: carboxymethyl chitosan (15 mg), Pluronic® F-127 (1.5% w/v), hyaluronic acid (0.2% w/v), HPMC (0.4% w/v), and carbopol 940 (1% w/v). SEM revealed a smooth, spherical, swollen, layered surface particle surface, ideal for wound interaction. The drug content ranged 97.3 ± 0.47% to 99.40 ± 0.10%. Ex vivo permeation showed steady-state flux of Neomycin (45.16 µg/cm²/h) and bromelain (36.78 µg/cm²/h) over 48 h from the Neom + Brom−loaded hydrogel. FTIR and XRD confirmed non-interacting drugs in molecular dispersion within the hydrogel composite. The Neom + Brom–loaded hydrogel-treated group showed significantly higher hydroxyproline levels (p < 0.05) on Day 15. This composite achieved greater wound closure efficacy than placebo or plain drug treatments on day 15 (visibly evident). Biochemical analysis of Neom + Brom − loaded hydrogel composite revealed elevated antioxidant biomarkers GPx, SOD, catalase), and reduced MDA levels in excised wound of Wistar rats, while the histopathology confirmed no infiltration of inflammatory cells, and increased collagen deposition versus controls, indicating accelerated wound healing.

Conclusion

The pH/temperature−responsive hydrogel composite shows promising potential as an effective wound healing therapy combining anti-inflammatory, and anti-oxidant and anti-bacterial properties to enhance tissue regeneration.