Chitosan-Coated PLGA Nanoparticles Loaded with Peganum harmala Alkaloids with Promising Antibacterial and Wound Healing Activities

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.

Synthesis, Characterization and Host-Guest Complexation of Asplatin: Improved In Vitro Cytotoxicity and Biocompatibility as Compared to Cisplatin

“…The stability constant of the asplatin/PSC4 inclusion complex found utilizing our previously reported method [16] was 9.1 × 104 M −1 , corresponding to a complexation free energy of −6.8 kcal mol −1 . This value is within the stability constant range (0.001 × 10 4 to 16 × 10 4 M -1 ) of host-guest complexes designed for drug delivery applications [29][30][31][32][33][34][35][36][37][38][39][40].…”

PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities

“…where S 0 is the intrinsic solubility, and K 1:1 is the stability constant. The designed HARF-HPßCD complex was co-loaded with AA into PLGA NPs coated with PEG (HARF-HPßCD/AA@PLGA-PEG NPs) using the W/O/W multiple emulsionsolvent evaporation method, as previously reported with some modifications [3,7,33,34].…”

“…Pharmaceutics 2022, 14, 142 2 of 13 The seeds of P. harmala are rich in harmala alkaloids such as quinazoline and β-carboline alkaloids. The major alkaloid, harmine, is responsible for the various pharmacological activities of the harmala seeds [5][6][7]. Several studies have reported the promising antimicrobial activities of P. harmala extracts [8,9].…”

The Expanded Role of Chitosan in Localized Antimicrobial Therapy

“…In this study, the chitosan-coated NPs were challenged against S. aureus and E. coli using in vitro broth dilution method. The loaded chitosan-coated NPs improved the antibacterial potential against E. coli and S. aureus [179]. In another research effort, chitosan-coated NPs comprising PLGA and PVA loaded with benzalkonium bromide were evaluated in an in vitro biofilm assay and an in vivo murine MRSA-infected wound model.…”