In Situ Hydrogel-Forming/Nitric Oxide-Releasing Wound Dressing for Enhanced Antibacterial Activity and Healing in Mice with Infected Wounds

Abstract

The eradication of bacteria from wound sites and promotion of healing are essential for treating infected wounds. Nitric oxide (NO) is desirable for these purposes due to its ability to accelerate wound healing and its broad-spectrum antibacterial effects. We developed an in situ hydrogel-forming/NO-releasing powder dressing (NO/GP), which is a powder during storage and forms a hydrogel when applied to wounds, as a novel NO-releasing formulation to treat infected wounds. An NO/GP fine powder (51.5 μm) was fabricated by blending and micronizing S-nitrosoglutathione (GSNO), alginate, pectin, and polyethylene glycol (PEG). NO/GP remained stable for more than four months when stored at 4 or 37 °C. When applied to wounds, NO/GP absorbed wound fluid and immediately converted to a hydrogel. Additionally, wound fluid triggered a NO release from NO/GP for more than 18 h. The rheological properties of hydrogel-transformed NO/GP indicated that NO/GP possesses similar adhesive properties to marketed products (Vaseline). NO/GP resulted in a 6-log reduction in colony forming units (CFUs) of methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, which are representative drug-resistant gram-positive and -negative bacteria, respectively. The promotion of wound healing by NO/GP was demonstrated in mice with full-thickness wounds challenged with MRSA and P. aeruginosa. Thus, NO/GP is a promising formulation for the treatment of infected wounds.

Semisolid Dosage

“…As third article on wound healing, Lee et al present results of ''In-Situ Hydrogel-Forming/Nitric Oxide-Releasing Wound Dressing for Enhanced Antibacterial Activity and Healing in Mice with Infected Wounds" [3]. The formulation is a dry powder consisting of alginate, pectin, PEG, and S-nitrosoglutathione, which shows good storage stability.…”

Nitric Oxide-Releasing S-Nitrosoglutathione-Conjugated Poly(Lactic-Co-Glycolic Acid) Nanoparticles for the Treatment of MRSA-Infected Cutaneous Wounds

“…In Figure 6 C, a large number of round-shaped, 1- to 2-μm-sized purple dots representing Gram-positive cocci (MRSA) were observed in GSNO-treated and untreated groups. In contrast, in healthy and GPNPs-treated groups, the purple dots were rarely seen, implying low levels of bacteria that were hard to detect by Gram staining [ 39 , 49 ]. Collectively, the GPNPs-treated group showed recovered morphology, with increased collagen deposition and tissue remodeling compared to the GSNO-treated and untreated groups as a result of enhanced bacterial removal from the wound site.…”

“…S-nitrosoglutathione (GSNO) is an endogenously synthesized NO donor that changes to glutathione (GSH) after releasing NO, the non-toxic and most abundant antioxidant in mammalian cells [ 35 , 36 ]. Due to its endogeneity, various GSNO formulations, such as hydrogels, films, and microparticles, have been developed as wound dressings [ 37 , 38 , 39 , 40 ]. However, until now, the fabrication of a nanoparticle formulation using GSNO has been challenging owing to the high hydrophilicity of GSNO, which remains a big hurdle to achieve sufficient loading of NO.…”

Dual stimuli-responsive polyurethane-based hydrogels as smart drug delivery carriers for the advanced treatment of chronic skin wounds

“…Topical drug administration directly in the wound site could represent an effective strategy to maximize the success of the treatment and improve patients' comfort while minimizing the therapeutic dose and, eventually, side effects. In this regard, many works have been reported on the design of drug delivery systems for the in situ release of anti-inflammatory drugs [ 1 , 2 ], anti-microbial agents [ 3 , 4 ] and biomolecules [ 5 , 6 ] for a more effective treatment of hard-to-close wounds. However, such systems generally lack control over drug release kinetics, thus reducing the potentialities of the localized drug administration route.…”