Thermoresponsive gels containing gold nanoparticles as smart antibacterial and wound healing agents

Abstract

Thermoresponsive gels containing gold nanoparticles (AuNPs) were prepared using Pluronic®127 alone (F1) and with hydroxypropyl methylcellulose (F2) at ratios of 15% w/w and 15:1% w/w, respectively. AuNPs were evaluated for particle size, zeta-potential, polydispersity index (PDI), morphology and XRD pattern. AuNP-containing thermoresponsive gels were investigated for their gelation temperature, gel strength, bio-adhesive force, viscosity, drug content, in vitro release and ex-vivo permeation, in addition to in vitro antibacterial activity against bacteria found in burn infections, Staphylococcus aureus. In vivo burn healing and antibacterial activities were also investigated and compared with those of a commercial product using burn-induced infected wounds in mice. Spherical AuNPs sized 28.9–37.65 nm displayed a surface plasmon resonance band at 522 nm, a PDI of 0.461, and a zeta potential of 34.8 mV with a negative surface charge. F1 and F2 showed gelation temperatures of 37.2 °C and 32.3 °C, bio-adhesive forces of 2.45 ± 0.52 and 4.76 ± 0.84 dyne/cm2, viscosities of 10,165 ± 1.54 and 14,213 ± 2.31 cP, and gel strengths between 7.4 and 10.3 sec, respectively. The in vitro release values of F1 and F2 were 100% and 98.03% after 6 h, with permeation flux values of (J1) 0.2974 ± 2.85 and (J2) 0.2649 ± 1.43 (µg/cm2·h), respectively. The formulations showed antibacterial activity with the highest values for wound healing properties, as shown in vivo and by histopathological studies. This study demonstrates that a smart AuNPs thermoresponsive gel was successful as an antibacterial and wound healing transdermal drug delivery system.

Antibiotic Delivery Strategies to Treat Skin Infections When Innate Antimicrobial Defense Fails

“…Because of the variety of microorganisms found in infected wounds, hydrogels that can deliver antibiotics or are inherently antimicrobial may provide critical wound treatment [15,22]. Various antimicrobial agents have been loaded into hydrogels for topical wound delivery, including gold and silver nanoparticles, fusidic acid, antimicrobial peptides, probiotic organisms, and other synthetic antimicrobial compounds [135][136][137][138][139][140]. Hydrogels can provide slow release of the antimicrobial agents over extended periods of time, which could decrease dressing change frequency and limit exposure to sub-inhibitory concentrations of antimicrobials.…”

“…Poloxamers (sold under the trade names Kolliphor, Pluronics, and Synperonics) are triblock copolymers with polyethylene oxide and polypropylene oxide segments [135,136,[176][177][178]. They have generated interest because they form thermoreversible hydrogels, meaning they are liquid at lower temperatures and transition to a gel at higher temperatures.…”

“…Desired drug release, degradation, adhesion, and mechanical properties of poloxamers can be achieved by incorporating other hydrogel components or crosslinking the network [179,180]. Arafa et al added hydroxypropyl methylcellulose to Pluronic ® F127 to improve gel strength and tune the release rate of antimicrobial gold nanoparticles [136]. The combination of hydroxypropyl methylcellulose and Pluronic led to a stronger gel, a lower gelation temperature, and reduced the burst-like release of gold nanoparticles compared to the Pluronic gel alone [136].…”

“…Arafa et al added hydroxypropyl methylcellulose to Pluronic ® F127 to improve gel strength and tune the release rate of antimicrobial gold nanoparticles [136]. The combination of hydroxypropyl methylcellulose and Pluronic led to a stronger gel, a lower gelation temperature, and reduced the burst-like release of gold nanoparticles compared to the Pluronic gel alone [136]. In a permeation study, both formulations showed the presence of the gold nanoparticles at the diffusion site for up to five hours.…”

<p>Silver Decorated Mesoporous Carbons for the Treatment of Acute and Chronic Wounds, in a Tissue Regeneration Context</p>

“…The employment of metallic nanoparticles can be particularly effective in regulating the different phases of the repair process and in promoting a faster wound closure, based on the specific ion properties. [8][9][10] Emphasis has been mainly placed so far on silver, which has been widely used in medicine for millennia due to its anti-bacterial and anti-inflammatory activity, having led to a variety of silver-containing formulations. 11 It has been shown that scaling down silver to the nanoscale (<100 nm) improves its antimicrobial activity compared with the bulk material due to the higher specific surface area.…”