pH-Responsive “Smart” Hydrogel for Controlled Delivery of Silver Nanoparticles to Infected Wounds

Abstract

Persistent wound infections have been a therapeutic challenge for a long time. Current treatment approaches are mostly based on the delivery of antibiotics, but these are not effective for all infections. Here, we report the development of a sensitive pH-responsive hydrogel that can provide controlled, pH-triggered release of silver nanoparticles (AgNPs). This delivery system was designed to sense the environmental pH and trigger the release of AgNPs when the pH changes from acidic to alkaline, as occurs due to the presence of pathogenic bacteria in the wound. Our results show that the prepared hydrogel restricts the release of AgNPs at acidic pH (pH = 4) but substantially amplifies it at alkaline pH (pH = 7.4 and pH = 10). This indicates the potential use of the hydrogel for the on-demand release of Ag+ depending on the environmental pH. In vitro antibacterial studies demonstrated effective elimination of both Gram-negative and positive bacteria. Additionally, the effective antibacterial dose of Ag+ showed no toxicity towards mammalian skin cells. Collectively, this pH-responsive hydrogel presents potential as a promising new material for the treatment of infected wounds.

Hybrid Collagen Hydrogel/Chondroitin-4-Sulphate Fortified with Dermal Fibroblast Conditioned Medium for Skin Therapeutic Application

“…Collagen in the form of hydrogel is suitable for various applications, including biomedical and tissue engineering, as it can absorb water molecules or swell when in contact with aqueous solutions due to the presence of hydrophilic groups in its backbone [47,48]. This would enable the diffusion of oxygen, proteins, and growth factors that are important in drug delivery, cell encapsulation, wound dressing, and tissue repair [47,49,50].…”

Eradication of Mature Bacterial Biofilms with Concurrent Improvement in Chronic Wound Healing Using Silver Nanoparticle Hydrogel Treatment

“…Cells treated with fresh DMEM were used as controls. After further incubation for 24 h, the cells were washed and resazurin dye was added and fluorescence intensity was measured after 2 h incubation at 37 • C. Cells that were grown and treated in glass coverslips were stained with Live/Dead staining according to the manufacturers' instructions, similar to our previous method [20]. Samples were imaged via Olympus IX81 epifluorescence microscope (Olympus, Tokyo, Japan).…”

“…The controlled release of Ag + from a hydrogel is another important aspect, as studies have shown that AgNPs have a short lifetime (3 h) while the inconsistent and fast release of Ag + contributes to high wound toxicity [ 18 ]. Consequently, the controlled release mechanism of AgNPs has been integrated with different delivery platforms i.e., antibacterial coatings [ 19 ], stimuli-responsive hydrogel to provide on-demand release [ 20 ], mussel-inspired hydrogels [ 21 ], and mesoporous silica nanoparticles with the slow dissolution of Ag + [ 22 ], many of which show promising in-vitro results. While their antibacterial activity is relatively well studied using in-vitro models, the AgNPs’ efficacy against mature biofilms in clinically relevant animal models is unconvincingly reported.…”

Hydrogels: 3D Drug Delivery Systems for Nanoparticles and Extracellular Vesicles

“…A recent study highlighted the potential of silver NPs loaded in pH responsive hydrogels as a potential candidate for wound healing. This was due to the unique property of switching to a hydrated state in the alkaline wound environment, resulting in the sustained release of silver NPs with antibacterial properties [65]. Another study assessing the efficacy of gold nanorods released from different hydrogels namely polyethylene glycol (PEG) and cationic poly allyl amine hydrochloride (PAH) demonstrated prominent wound healing ability with complete closure of the wound within 14 days of the treatment along with improved skin re-epithelialization and collagen formation as well as noticeable impact on the inflammatory gene expression [79].…”