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.

Highlights

  • Skin burns are one of the major causes of morbidity and mortality in burn patients due to susceptibility to infection

  • Transmission electron microscopy (TEM) analysis was performed to comprehend the shapes and sizes of the AuNPs, and the results showed the formation of triangular to spherical nanoparticles 28.9–37.65 nm in size, with no aggregation (Fig. 1d)

  • The X-ray diffraction (XRD) patterns of the AuNPs were recorded in a spectrum of 2θ from 10° to 70°, and the results showed the presence of the three characteristic intense peaks of 31.7°, 45.4° and 67.7°, corresponding to the (111), (200) and (220) planes of the face-centred cubic AuNPs

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Summary

Introduction

Skin burns are one of the major causes of morbidity and mortality in burn patients due to susceptibility to infection. The widespread use of antibacterial agents for the treatment of skin infections, including burns, in hospitals has favoured the emergence of multidrug resistant bacteria, such as Klebsiella sp. Nanotechnology has acquired its importance by using nanomaterials, which have enormous biological applications in various medical fields, including biomedicine[4], pharmacology, parasitology, nanopharmaceutics and drug delivery systems[5,6,7,8,9]. The antibacterial effect of AuNPs has recently been an interesting research area, which makes them suitable for the potential complementary use with antibiotics[13,14]. Administered antibiotics can encounter difficulties reaching damaged skin tissue due to compromised blood circulation, making them ineffective for reducing bacterial counts in granulation wounds[17]. The use of topically applied antibacterial products is preferable, due to the controlled effects, low systemic toxicity, ease of application, patient compliance and the avoidance of the first-pass effect[18]

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