RESUMEN
Topical nitric oxide (NO) delivery has been shown to accelerate wound healing. However, delivering NO to wounds at appropriate rates and doses requires new biomaterial-based strategies. Here, we describe the development of supramolecular interpolymer complex hydrogels comprising PEO-PPO-PEO (F127) micelles embedded in a poly(acrylic acid) (PAA) matrix, with S-nitrosoglutathione (GSNO) molecules dissolved in the hydrophilic domain. We show that PAA:F127/GSNO hydrogels start releasing NO upon hydration at rates controlled by their rates of water absorption. SAXS measurements indicate that the supramolecular structure of the hydrogels retains long-range order domains of F127 micelles. The PAA/F1227 hydrogels displayed dense morphologies and reduced rates of hydration. The NO release rates remain constant over the first 200â¯min, are directly correlated with the hydration rates of the PAA:F127/GSNO hydrogels, and can be modulated in the range of 40â¯nmol/gâ¯h to 1.5⯵mol/gâ¯h by changing the PAA:F127 mass ratio. Long-term NO-release profiles over 5â¯days are governed by the first-order exponential decay of GSNO, with half-lives in the range of 0.5-3.4â¯days. A preliminary in vivo study on full-thickness excisional wounds in mice showed that topical NO release from the PAA:F127/GSNO hydrogels is triggered by exudate absorption and leads to increased angiogenesis and collagen fiber organization, as well as TGF-ß, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue. In summary, these results suggest that hydration-controlled NO release from topical PAA:F127/GSNO hydrogels is a potential strategy for enhancing wound healing. STATEMENT OF SIGNIFICANCE: The topical delivery of nitric oxide (NO) to wounds may provide significant beneficial results and represent a promising strategy to treat chronic wounds. However, wound dressings capable of releasing NO after application and allowing the modulation of NO release rates, demand new platforms. Here, we describe a novel strategy to overcome these challenges, based on the use of supramolecular poly(acrylic acid) (PAA):F127 hydrogels charged with the NO donor S-nitrosoglutathione (GSNO) from whereby the NO release can be triggered by exudate absorption and delivered to the wound at rates controlled by the PAA:F127 mass ratio. Preliminary in vivo results offer a proof of concept for this strategy by demonstrating increased angiogenesis; collagen fibers organization; and TGF-ß, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue after topical treatment with a PAA:F127/GSNO hydrogel.
Asunto(s)
Resinas Acrílicas , Hidrogeles , Óxido Nítrico , Polietilenos , Polipropilenos , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones , Resinas Acrílicas/farmacocinética , Resinas Acrílicas/farmacología , Animales , Citocinas/biosíntesis , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacocinética , Hidrogeles/farmacología , Ratones , Micelas , Óxido Nítrico/química , Óxido Nítrico/farmacocinética , Óxido Nítrico/farmacología , Polietilenos/química , Polietilenos/farmacocinética , Polietilenos/farmacología , Polipropilenos/química , Polipropilenos/farmacocinética , Polipropilenos/farmacología , S-Nitrosoglutatión/química , S-Nitrosoglutatión/farmacocinética , S-Nitrosoglutatión/farmacología , Heridas y Lesiones/tratamiento farmacológico , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patologíaRESUMEN
This paper introduces cotton fibers impregnated with biogenic silver nanoparticles (AgNPs), synthesized from a Fusarium oxysporum fungal filtrate (FF) solution, and open up the possibility for their use in medical environment and agriculture clothing as means to avoid microbial spreading. After thorough AgNPs characterization, regarding their physical, chemical and biochemical properties, Minimum Inhibitory Concentrations (MIC) against some human and orange tree pathogens were determined. We report the strong AgNPs activity against Candida parapsilosis and Xanthomonas axonopodis pv. citri (Xac) that was morphologically characterized, pointing to strong AgNPs effects on microorganisms' membranes. Cotton fibers were then impregnated with AgNPs suspension and these maintained strong antimicrobial activity even after repeated mechanical washing cycles (up to 10). Reported data might point to an application for biogenic AgNPs as potent agrochemicals, as well as, to their application in textiles for antiseptic clothing for medical and agronomic applications.