Abstract
Wound healing is a major healthcare concern, and complicated wounds may lead to severe outcomes such as septicemia and amputations. To date, management choices are limited, which warrants the search for new potent wound healing agents. Natural products loaded in poly (lactic-co-glycolic acid) (PLGA) coated with chitosan (CS) constitute a promising antibacterial wound healing formulation. In this work, harmala alkaloid-rich fraction (HARF) loaded into PLGA nanoparticles coated with chitosan (H/CS/PLGA NPs) were designed using the emulsion-solvent evaporation method. Optimization of the formulation variables (HARF: PLGA and CS: PLGA weight ratios, sonication time) was performed using the 33 Box–Behnken design (BBD). The optimal NPs were characterized using transmission electron microscopy (TEM) and Attenuated Total Reflection Fourier-Transformed Infrared Spectroscopy (ATR-FTIR). The prepared NPs had an average particle size of 202.27 ± 2.44 nm, a PDI of 0.23 ± 0.01, a zeta potential of 9.22 ± 0.94 mV, and an entrapment efficiency of 86.77 ± 4.18%. In vitro drug release experiments showed a biphasic pattern where an initial burst of 82.50 ± 0.20% took place in the first 2 h, which increased to 87.50 ± 0.50% over 72 h. The designed optimal H/CS/PLGA NPs exerted high antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.125 and 0.06 mg/mL, respectively) compared to unloaded HARF (MIC of 0.50 mg/mL). The prepared nanoparticles were found to be biocompatible when tested on human skin fibroblasts. Moreover, the wound closure percentage after 24 h of applying H/CS/PLGA NPs was found to be 94.4 ± 8.0%, compared to free HARF and blank NPs (68.20 ± 5.10 and 50.50 ± 9.40%, respectively). In conclusion, the three components of the developed nanoformulation (PLGA, chitosan, and HARF) have synergistic antibacterial and wound healing properties for the management of infected wounds.
Highlights
PLGA is an outstanding carrier for different wound healing agents because of its ability to adhere to the wound surface while releasing the loaded drug in a controlled manner [28]
No statistically significant difference in cell viability was observed for H/CS/PLGA NPs compared to the control (p < 0.05)
The scratch wound healing assay was used to study the in vitro wound healing capabilities using human skin fibroblast cells. This assay was performed to observe the effect of the optimized H/CS/PLGA NPs on the healing process, compared to free harmala alkaloid-rich fraction (HARF), and a blank CS/PLGA NPs formulation was used as a control
Summary
One of the significant issues that can delay wound healing/closure is infection with Gram-positive and/or Gram-negative bacteria such as Staphylococcus aureus and Escherichia coli, respectively These pathogens can infect deep skin tissues in chronic wounds, leading to the Nanomaterials 2021, 11, 2438. Nanomaterials 2021, 11, 2438 perturbation of the physiological wound healing process [3,4] Natural products such as plant extracts have drawn much attention in the remedy of many diseases [5,6,7]. Some natural and synthetic polymers were found to have healing properties by improving proliferation and increasing the cell count. PLGA is an outstanding carrier for different wound healing agents because of its ability to adhere to the wound surface while releasing the loaded drug in a controlled manner [28]. The antimicrobial and wound healing properties of H/CS/PLGA NPs were studied, and their cytotoxicity was evaluated
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