Antibiofilm Potential of Silver Sulfadiazine-Loaded Nanoparticle Formulations: A Study on the Effect of DNase-I on Microbial Biofilm and Wound Healing Activity

Abstract

Biofilm resistance is one of the severe complications associated with chronic wound infections, which impose extreme microbial tolerance against antibiotic therapy. Interestingly, deoxyribonuclease-I (DNase-I) has been empirically proved to be efficacious in improving the antibiotic susceptibility against biofilm-associated infections. DNase-I hydrolyzes the extracellular DNA, a key component of the biofilm responsible for the cell adhesion and strength. Moreover, silver sulfadiazine, a frontline therapy in burn wound infections, exhibits delayed wound healing due to fibroblast toxicity. In this study, a chitosan gel loaded with solid lipid nanoparticles of silver sulfadiazine (SSD-SLNs) and supplemented with DNase-I has been developed to reduce the fibroblast cytotoxicity and overcome the biofilm-imposed resistance. The extensive optimization using the Box–Behnken design (BBD) resulted in the formation of SSD-SLNs with a smooth surface as confirmed by scanning electron microscopy and controlled release (83%) for up to 24 h. The compatibility between the SSD and other formulation excipients was confirmed by Fourier transform infrared, differential scanning calorimetry, and powder X-ray diffraction studies. Developed SSD-SLNs in combination with DNase-I inhibited around 96.8% of biofilm of Pseudomonas aeruginosa as compared to SSD with DNase-I (82.9%). In line with our hypothesis, SSD-SLNs were found to be less toxic (cell viability 90.3 ± 3.8% at 100 μg/mL) in comparison with SSD (Cell viability 76.9 ± 4.2%) against human dermal fibroblast cell line. Eventually, the results of the in vivo wound healing study showed complete wound healing after 21 days’ treatment with SSD-SLNs along with DNase-I, whereas marketed formulations SSD and SSD-LSNs showed incomplete healing after 21 days. Data in hand suggest that the combination of SSD-SLNs with DNase-I is an effective treatment strategy against the biofilm-associated wound infections and accelerates wound healing.

Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications

“…In addition, deoxyribonuclease-I was demonstrated to disrupt the extracellular DNA of the biofilm increasing the action range of silver sulfadiazine. In vivo tests showed an acceleration on wound healing and complete re-epithelization of skin, thus confirming the superiority of the proposed therapy when compared with the current treatments [41].…”

“…The treatment group includes (i) untreated (diseased control); (ii) silver sulfadiazine marketed cream; (iii) Silver sulfadiazine-loaded solid lipid nanoparticles-containing chitosan gel; (iv) Silver sulfadiazine-loaded solid lipid nanoparticles and DNase-I-containing chitosan gel. Reproduced from Patel et al [41].…”

Intervening in Symbiotic Cross-Kingdom Biofilm Interactions: a Binding Mechanism-Based Nonmicrobicidal Approach

“…Target specificity and retention of antibiofilm agents, as well as their penetration behaviors into the biofilm, may determine the fate of the antibiofilm strategy (35). For example, enhanced retention of antibacterial agent-loaded nanoparticles resulted in a dramatic improvement in antibiofilm activity, compared with the non-loaded antibacterial agent (36)(37)(38). Thus, enhanced retention and penetration of MDEs may further improve the efficacy of this approach.…”

Promising Therapeutic Strategies Against Microbial Biofilm Challenges

“…These biofilm-dispersing enzymes have better antimicrobial activities when administered in combination with antimicrobial agents (Darouiche et al, 2009 ; Rodríguez-López et al, 2017 ; Kim et al, 2019 ; Eladawy et al, 2020 ). Researchers have also tried different enzyme combinations (Karygianni et al, 2020 ) or dispersal-inducing enzymes combined with other new technologies, such as nanotechnology (Patel et al, 2019 ; Tasia et al, 2020 ), to improve antimicrobial biofilm activity and achieve good results. Thus, enzymatic treatment combined with conventional antimicrobial agents or other novel antibiofilm therapeutic agents provides us with another effective treatment strategy against biofilm-associated infections aimed at both bactericidal effectiveness and biofilm dispersal.…”