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. 2020 Sep 28;12(10):926.
doi: 10.3390/pharmaceutics12100926.

Nitric Oxide-Releasing Thermoresponsive Pluronic F127/Alginate Hydrogel for Enhanced Antibacterial Activity and Accelerated Healing of Infected Wounds

Jiafu Cao  1 , Mingzhi Su  1 , Nurhasni Hasan  1 , Juho Lee  1 , Dongmin Kwak  1 , Dong Young Kim  2 , Keonwoo Kim  2 , Eun Hee Lee  2 , Jee H Jung  1 , Jin-Wook Yoo  1
Affiliations

Nitric Oxide-Releasing Thermoresponsive Pluronic F127/Alginate Hydrogel for Enhanced Antibacterial Activity and Accelerated Healing of Infected Wounds

Jiafu Cao et al. Pharmaceutics. .

Abstract

Nitric oxide (NO), a highly reactive and lipophilic molecule, is one of the molecules present in the wound environment and implicated as an important regulator in all phases of wound healing. Here, we developed an NO-releasing thermoresponsive hydrogel (GSNO-PL/AL) composed of S-nitrosoglutathione (GSNO), pluronic F127 (PL), and alginate (AL) for the treatment of infected wounds. The GSNO was incorporated into the thermoresponsive PL/AL hydrogel, and differential scanning calorimetry techniques were used for the hydrogel characterization. The hydrogel was assessed by in vitro NO release, antibacterial activity, cytotoxicity, and wound-healing activity. The GSNO-PL/AL hydrogel demonstrated thermal responsiveness and biocompatibility, and it showed sustained NO release for 7 days. It also exhibited potent bactericidal activity against Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative multidrug-resistant Pseudomonas aeruginosa (MRPA). Moreover, the GSNO-PL/AL treatment of MRPA-infected wounds accelerated healing with a reduced bacterial burden in the wounds. The GSNO-PL/AL hydrogel would be a promising option for the treatment of infected wounds.

Keywords: S-nitrosoglutathione; antibacterial; infected wound healing; pluronic F127; thermoresponsive.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram of GSNO-PL/AL hydrogel synthesis and sol−gel transition. AL: alginate, GSNO: S-nitrosoglutathione, PL: pluronic F127.
Figure 2
Figure 2
(A) Temperature ramp test of PL/AL and GSNO-PL/AL. Changes of storage modulus (G′) and loss modulus (G″) as the temperature changes. (B) Differential scanning calorimetry (DSC) thermographs of PL, PL/AL, and GSNO-PL/AL hydrogels.
Figure 3
Figure 3
The nitric oxide (NO) release profile from the GSNO-PL/AL hydrogel. The black-colored line shows the real-time monitoring of NO release (ppb/mg) from GSNO-PL/AL hydrogel detected every five seconds; the red-colored line shows the percentage of NO release from the GSNO-PL/AL hydrogel.
Figure 4
Figure 4
In vitro viability of L929 fibroblast cells after incubating for 24 h with hydrogels at various concentrations. Data shown are mean ± S.D. (n = 6).
Figure 5
Figure 5
In vitro antibacterial activities of PL/AL and GSNO-PL/AL hydrogels against (A) multidrug-resistant Pseudomonas aeruginosa (MRPA) and (B) methicillin-resistant Staphylococcus aureus (MRSA). (C) Side-view schematic of antimicrobial study configuration using agar plate with bacterial growth. Macroscopic images of antibacterial activities on the agar plate against (D) MRPA and (E) MRSA.
Figure 6
Figure 6
(A) Representative photographs of healing burn wounds infected with MRPA in mice treated with PL/AL and GSNO-PL/AL. (B) Area reduction (%) profiles of MRPA-infected wounds. Data are presented as means ± SD; n = 6. * p < 0.05 vs. untreated. (C) Histological analysis (hematoxylin and eosin (H & E) and Masson’s trichrome staining) of MRPA-infected wound at 11 days after injury. Bar = 100 µm.
Figure 7
Figure 7
Bacterial burden in wounds at 11 days after injury. * p < 0.05 vs. untreated.
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