A mucoadhesive collagen hydrogel co-delivering adipose-derived stem cells and quercetin nanoparticles for allergic rhinitis

Limited nasal residence time with topical administration of medications can lead to poor effectiveness of local treatment options for allergic rhinitis (AR) due to rapid mucosal clearance and the need for frequent dosing. Novel polymeric co-delivery platforms capable of locally treating inflammation and providing prolonged bioactivity have emerged that combine controlled-release drug depots with therapeutic cells. Quercetin-loaded chitosan nanoparticles (QCT-CNPs) were synthesized via ionotropic gelation then characterized for encapsulation efficiency (EE%), loading capacity (LC%), release kinetics in PBS (pH 7.4) over 72 h, and morphology/size by SEM. Collagen hydrogels containing ASCs and QCT-CNPs were fabricated and characterized for ASC metabolic activity (basal and H₂O₂ stimulated), swelling, DPPH radical-scavenging activity, anti-inflammatory activity using LPS-stimulated RAW 264.7 macrophages (IL-6 and TNF-α), and in vitro mucoadhesion on a mucin substrate. Hydrogel formulation groups were then compared in an ovalbumin-induced rat AR model using histology (H&E staining and Masson's trichrome), blinded histomorphometry, and nasal-tissue ELISA assay. Formulated QCT-CNPs had an EE% of 38.91 ± 8.07% and LC% of 8.08 ± 1.93%. Sustained release kinetics increased linearly to 91.637 ± 3.415% release at 72 h. SEM analysis of nanoparticles revealed mostly spherical morphology with particle size increasing from 130.4 ± 32.29 nm for blank CNPs to 176.1 ± 42.21 nm for QCT-CNPs. COL-ASCs-QCT-1 formulation consistently produced improvements in mucosal histology and histomorphometric indices in vivo, and significantly reduced tissue inflammatory mediator levels, comparable to other formulations. Localized co-delivery of ASCs and sustained-release QCT-CNPs using a collagen hydrogel represents a promising approach to treat AR by harnessing prolonged mucosal retention time with multi-modal anti-inflammatory and tissue-supportive activity.