Sinonasal Delivery of Resveratrol via Mucoadhesive Nanostructured Microparticles in a Nasal Polyp Mouse Model

Abstract

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.

Effect of lipopolysaccharide and polyinosinic:polycytidylic acid in a murine model of nasal polyp

“…For the histopathological analysis, the heads of five mice per group were collected. Detailed experimental procedures have been previously described 46,47 . Different protocols were used www.nature.com/scientificreports/ to evaluate the degrees of inflammation, polyp formations, and epithelial disruptions.…”

How to characterize a nasal product. The state of the art of in vitro and ex vivo specific methods

“…This method was selected to highlight the mucoadhesion when developing resveratrol-loaded microparticles with either PLGA or a PLGA/PEG combination. With the PLGA/PEG combination, 81.96 ± 1.86 μg of mucins per mg of microparticles were fixed, while PLGA microparticles showed a lower binding of 70.13 ± 2.18 μg of mucins per mg of microparticles (Lee et al, 2017). This test was therefore very useful to show the interest of the combination of both excipients.…”

Crosstalk Between Mucosal Inflammation and Bone Metabolism in Chronic Rhinosinusitis

“…The presence of osteitis was identified by changes in periosteal thickening, osteoblastic and osteoclastic activity, and woven bone formation in sections used for histologic scoring. Murine models have been used to study the pathophysiology of CRS in several recent studies [69][70][71][72][73][74][75]. Mice have several advantages over rabbits as a model of CRS, including the availability of reagents to explore immunological responses and the availability of many knockout and transgenic models.…”