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.
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