Coumarin/nitrogen-bearing heterocyclic hybrid-loaded electrospun PMMA/PVP nanofibrous scaffolds for accelerating topical wound healing rates: synthesis and <i>in vitro</i> bio-evaluation

Coumarin-nitrogen heterocyclic compounds (<i>e.g.</i> quinoline, acridine, and phthalazine) were synthesized by facile reactions and elucidated by FTIR, ¹H, and ¹³C-NMR analyses, which showed consistency with the expected structures. Coumarin-quinoline (drug A)- and coumarin-acridine (drug B)-loaded electrospun PMMA/PVP nanofibrous scaffolds were fabricated using electrospinning techniques. Results showed a successful PMMA/PVP blend, which formed the matrix that was used as the main scaffold for drug loading/release. The drugs (A and B) were encapsulated within the matrix as verified by IR and SEM results. Bio-evaluation through cytotoxicity and anticancer screening was conducted using the MTT assay against lung fibroblast (Wi-38), colon carcinoma (Caco-2), lung carcinoma (A549) and breast carcinoma (MDA) cell lines. Notably, the IC₅₀ values of the synthesized derivatives against Wi-38 cells were found in the range of 126.3-195.0 μg mL^-1, indicating a high level of safety for the synthesized compounds toward the treated human normal (Wi-38) cell line. The IC₅₀ values of these potent derivatives against Caco-2 cells were estimated in the range of 4.87-38.23 μg mL^-1, with SI values ranging from 4.59 to 25.93. Their IC₅₀ values against A549 cells were estimated to be in the range of 5.74-32.05 μg mL^-1, with SI values ranging from 5.47 to 18.09. However, their IC₅₀ values against MDA cells were estimated to be in the range of 4.27-14.91 μg mL^-1, with SI values ranging from 11.76 to 29.58 μg mL^-1. The antimicrobial activities of the two synthesized compounds toward Gram-positive compared to Gram-negative bacteria were estimated; the highest antimicrobial activity was achieved at inhibition zones of ∼19.5 ± 2.3 and 17.2 ± 1.3 mm toward <i>S. aureus</i> and <i>S. mutans</i>, respectively, followed by <i>S. typhimurium</i> (∼15.5 ± 1.1 mm). According to the obtained findings, coumarin-nitrogen heterocyclic compounds (quinoline, acridine)-loaded PMMA/PVP electrospun NFs can be regarded as good antimicrobial biomaterials for different biomedical applications, particularly for wound dressings.