Construction of PLGA nanoparticles modified with RWrNM and DLPC and their application in acute rhinosinusitis

In an effort to overcome the nasal mucus barrier and epithelial barrier, as well as reduce entry into the bloodstream, we designed RWrNM and DLPC-modified PLGA nanoparticles (PDR-NPs). These nanoparticles were further encapsulated with dexamethasone acetate (Dexac) to form Dexac/PDR-NPs. Transmission electron microscopy (TEM) analysis revealed their spherical shape with an outer lipid layer. Dynamic light scattering (DLS) determined their particle size to be 125.77 ± 2.01 nm, with a polydispersity index (PDI) of 0.139 ± 0.029. The experimental results demonstrate that DLPC-modified PLGA nanoparticles can effectively reduce interactions with mucin at different concentrations, decrease aggregation, and facilitate their crossing of the mucus barrier. Additionally, results from the cellular uptake assay revealed a significantly greater uptake of PDR-NPs by inflammatory RAW 264.7 cells (2.99-fold higher than that of free C6, p < 0.0001) and inflammatory HUVECs (7.20-fold higher than that of free C6, p < 0.0001). Furthermore, Dexac/PDR-NPs effectively reduced the levels of inflammatory factors nitric oxide (NO) (p < 0.001) and interleukin-6 (IL-6) (p < 0.05) in the supernatant of inflammatory RAW 264.7 cells. Intravital imaging of rats revealed that PDR-NPs had a longer residence time in inflamed nasal tissue compared to PD-NPs. Furthermore, in vivo pharmacodynamic experiments showed that Dexac/PDR-NPs effectively reduced the symptoms of nasal inflammation, lowered the pH of nasal secretions, decreased serum inflammatory factor levels (TNF-α and IL-6), and reduced nasal mucosal inflammatory factor levels (IL-1β), while also reducing the degree of inflammation in the nasal mucosa. Both cytotoxicity assays and in vivo results indicate that PDR-NPs have a good safety profile. PDR-NPs not only overcome the nasal mucus barrier but also reduce the systemic toxicities associated with drug entry into the circulation by enhancing the targeting of inflammatory macrophages and inflammatory vascular endothelial cells. PDR-NPs allow for an "open sources and cut costs" treatment strategy to increase drug retention in the inflamed nasal tissues, reducing toxicity and increasing efficacy. In conclusion, PDR-NPs can be a promising drug delivery system for the local treatment of acute rhinosinusitis.