Design and construction of a silver(I)-loaded cellulose-based wound dressing: trackable and sustained release of silver for controlled therapeutic delivery to wound sites

Abstract

Although application of silver nitrate and silver sulfadiazine have been shown to be effective in thwarting infections at burn sites, optimization of the delivery of bioactive silver (Ag+) remains as an obstacle due to rapid precipitation and/or insolubility of the silver sources. To circumvent these shortcomings, we have designed a silver(I) complex [Ag(ImD)2]ClO4 (ImD = dansyl imidazole) that effectively increases the bioavailability of Ag+ and exhibits MIC values of 2.3 and 4.7 μg/mL against E. coli and S. aureus, respectively. This fluorescent silver complex has been incorporated within a robust hydrogel derived from carboxymethyl cellulose that allows slow release of silver. A complete occlusive dressing has finally been constructed with the Ag(ImD)CMC (1 % Ag loaded) pad sealed between a sterile mesh gauze (as bottom layer) and a rayon-based surgical tape (as the top layer). Such construction has afforded a dressing that displays sustained delivery of silver onto a skin and soft tissue infection model and causes effective eradication of bacterial loads within 24 h. The transfer of the bioactive silver complex is readily visualized by the observed fluorescence that overlays precisely with the kill zone. The latter feature introduces a unique feature of therapeutic trackability to this silver-donating occlusive dressing.

Chemical Modification of Bacterial Cellulose for the Development of an Antibacterial Wound Dressing

“…A very common example of active compounds is represented by metal ions. In this context, silver is probably the most common metal, and it has been incorporated into BC in different forms such as salts ( Chen et al, 2019 ), bound to zeolites ( Gupta et al, 2016 ) or montmorillonite ( Horue et al, 2020 ), silver-based fluorescent complex (namely, [Ag(ImD) 2 ]ClO 4 ) ( DeBoer et al, 2015 ) and silver sulfadiazine ( Faisul Aris et al, 2019 ). Other metals have also been explored for this purpose, in particular, the introduction of zinc and zinc oxide has been investigated ( Janpetch et al, 2016 ; Shahmohammadi Jebel and Almasi, 2016 ; Khalid et al, 2017 ; Wahid et al, 2019a ; Dharmalingam and Anandalakshmi, 2020 ; Dincă et al, 2020 ) as well as titanium oxide ( Khan et al, 2015 ; Ullah et al, 2016 ).…”

Contribution of Topical Agents to Wound Healing

“…In its ionized form (Ag + ) silver can interfere with thiol (-SH) groups, promote the production of reactive oxygen species (ROS) and bind to bacterial DNA and RNA. Through these mechanisms it causes structural changes to the bacterial cell wall, intracellular and nuclear membranes, disrupts the production of ATP and inhibits replication, ultimately leading to the loss of function and cell death [4][5][6][7][8]. Silver ion-release products are effective against various bacteria, including methicillin-resistant S. aureus (MRSA) and vancomycin resistant enterococcus (VRE) [4], fungi and viral pathogens [9].…”

“…While ionic silver has the highest therapeutic capacity, it is also rapidly inactivated after being applied to a wound due to its high nonspecific reactivity [7]. Instead, nanoparticles of silver have been used in modern wound dressings, combining a large active surface area and a degree of control over the rate of Ag + release into the wound [7,8]. Silver wound dressings have been developed in several ways, some binding nanocrystalline silver to carbon fibers, attaching it to polyurethane foam, attaching it to hydrocellular foam and coating it over polyethylene.…”

The Impact of Engineered Silver Nanomaterials on the Immune System

“…DeBoer et al designed a silver (I) complex incorporated within carboxymethyl cellulose hydrogel that allowed slow release of silver. The hydrogel increased the bioavailability of Ag + and achieving MIC values of 4.7 and 2.3 µg/mL against S. aureus and Escherichia coli , respectively [ 156 ]. Evaluation of Acticoat silver-based dressings was conducted in a rabbit model with muscle injury contaminated by S. aureus [ 157 ].…”