stilbenes and Rhinitis

Resveratrol (RSV) has been shown to effectively suppress chronic rhinosinusitis with nasal polyps in a mouse model; however, when locally administered to the sinonasal cavity, bolus RSV is limited by low drug bioavailability owing to its low aqueous solubility and relatively rapid clearance from the administration site. To address this limitation, we propose mucoadhesive nanostructured microparticles (PLGA/PEG NM) as a potential carrier for the sinonasal delivery of RSV. In this study, PLGA/PEG NM released RSV in a sustained manner. Owing to the enlarged specific surface area of the nanostructures, PLGA/PEG NM had synergistically enhanced mucoadhesiveness and thus showed improved in vivo retention properties in the sinonasal cavity. Therefore, when tested in a mouse nasal polyp model, PLGA/PEG NM mitigated polyp formation and restored epithelial integrity better than the control treatments. The therapeutic effect was similar at half the dose of PLGA/PEG NM, suggesting improved local bioavailability of RSV in the sinonasal cavity.

Topics: Adhesives; Administration, Intranasal; Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Carriers; Male; Mice, Inbred BALB C; Nanoparticles; Nasal Mucosa; Nasal Polyps; Resveratrol; Rhinitis; Sinusitis; Stilbenes

Since the recent establishment of a murine model of eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), both the development of new drugs for treatment or prevention of eosinophilic CRSwNP and elucidation of their pathogenesis have been feasible. We investigated the therapeutic effects of resveratrol on CRSwNP and its mechanism of action using a murine model.. After induction of eosinophilic CRSwNP, the therapeutic effects of resveratrol were tested and compared with those of triamcinolone acetonide. Histopathologic changes were evaluated using hematoxylin and eosin for overall inflammation, Sirius red for eosinophils, and Masson's trichrome stain for collagen. The expression levels of the interleukin (IL)-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase genes were assessed by quantitative real-time PCR. Cyclooxygense-2 and 5-lipoxygense levels were evaluated by immunohistochemical staining and Western blot analysis.. The degree of eosinophilic infiltration and subepithelial fibrosis was significantly decreased by administration of high-dose resveratrol, the potency of which was similar to that of triamcinolone acetonide. The expression levels of the IL-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase genes were significantly decreased by administration of low- or high-dose resveratrol. The production of 5-lipoxygenase was strongly inhibited by high-dose resveratrol.. Resveratrol may be useful for the prevention of eosinophilic CRSwNP. A key mechanism of its action is believed to be its anti-inflammatory effect, particularly on eosinophils, by inhibiting the lipoxygenase pathway.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biopsy, Needle; Blotting, Western; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Eosinophilia; Immunohistochemistry; Mice; Mice, Inbred BALB C; Nasal Polyps; Random Allocation; Real-Time Polymerase Chain Reaction; Reference Values; Resveratrol; Rhinitis; Risk Assessment; Sinusitis; Statistics, Nonparametric; Stilbenes; Treatment Outcome