Unlocking the potential of PLGA/thymoquinone nanoparticles: a promising frontier in asthma therapeutics

Objective(s): To formulate mPEG-PLGA/Thymoquinone nanoparticles for enhanced biological uptake and therapeutic effectiveness of thymoquinone in asthmatic mice induced with ovalbumin (OVA) administration.Materials and Methods: mPEG-PLGA/thymoquinone nanoparticles generated using nanoprecipitation were studied for size distribution (dynamic light scattering), in vitro release profile, drug entrapment efficiency (EE), and appearance (scanning electron microscopy). Cytotoxicity assessment via the MTT assay using L929 and RAW 264.7, (a mouse macrophagic cell line) confirmed that the formulation was biocompatible at concentrations up to 1000 µg/m. Drug release was analyzed at 37°C and 25°C over 8 days. In vivo efficacy was evaluated in mice with OVA-induced asthma, measuring OVA-specific IgE and cytokine levels (IL-4, IL-13), and lung histopathology (H&E staining).Results:The nanoparticles exhibited an average size of 255 nm and EE of 68.16%. In vitro release showed early rapid discharge with a subsequent gradual course. In vivo, mPEG-PLGA/Thymoquinone significantly reduced serum OVA-specific IgE levels and Th2-type cytokines (IL-13 and IL-4) in bronchoalveolar lavage fluid (BALF) compared to PBS and thymoquinone treatments. Histopathological analysis (H&E staining) confirmed that mPEG-PLGA/Thymoquinone significantly reduced perivascular and peribronchial inflammation, edema, and epithelial thickness, demonstrating superior efficacy compared to Dexamethasone and free Thymoquinone in some parameters.Conclusion: mPEG-PLGA/Thymoquinone nanoparticles provide an effective strategy for enhancing thymoquinone's therapeutic potential in asthma by improving drug delivery, reducing inflammation, and modulating the immune response.