一种共递送脂肪来源干细胞和槲皮素纳米颗粒的黏膜黏附性胶原水凝胶用于过敏性鼻炎

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中文摘要

背景： 局部给药时鼻腔停留时间有限，可因黏膜快速清除和需要频繁给药而导致过敏性鼻炎（AR）局部治疗方案效果不佳。新型聚合物共递送平台能够局部治疗炎症并提供持久生物活性，已将控释药物储库与治疗性细胞相结合。方法：通过离子型凝胶化合成负载槲皮素的壳聚糖纳米颗粒（QCT-CNPs），然后对其包封率（EE%）、载药量（LC%）、在PBS（pH 7.4）中72小时的释放动力学以及通过SEM观察的形态/粒径进行表征。制备含有ASCs和QCT-CNPs的胶原水凝胶，并对其ASC代谢活性（基础和H₂O₂刺激）、溶胀、DPPH自由基清除活性、使用LPS刺激的RAW 264.7巨噬细胞（IL-6和TNF-α）评估的抗炎活性以及在黏蛋白基质上的体外黏膜黏附性进行表征。随后在卵清蛋白诱导的大鼠AR模型中比较各水凝胶制剂组，使用组织学（H&E染色和Masson三色染色）、盲法组织形态计量学和鼻组织ELISA测定。结果：配制的QCT-CNPs的EE%为38.91 ± 8.07%，LC%为8.08 ± 1.93%。持续释放动力学呈线性增加，72小时释放达91.637 ± 3.415%。纳米颗粒的SEM分析显示主要为球形形态，粒径从空白CNPs的130.4 ± 32.29 nm增加至QCT-CNPs的176.1 ± 42.21 nm。COL-ASCs-QCT-1制剂在体内持续改善黏膜组织学和组织形态计量学指标，并显著降低组织炎症介质水平，与其他制剂相当。结论：使用胶原水凝胶局部共递送ASCs和缓释QCT-CNPs，通过利用延长的黏膜停留时间以及多模式抗炎和组织支持活性，代表了一种有前景的AR治疗方法。

英文摘要

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.