Nasal administration of polysaccharides-based nanocarrier combining hemoglobin and diferuloylmethane for managing diabetic kidney disease

Abstract

The management of diabetic kidney disease (DKD) faces challenges stemming from intricate pathologies and suboptimal biodistributions during drug delivery. Although clinically available anti-inflammatory agents hold considerable promise for treating DKD, their therapeutic effectiveness is limited when utilized in isolation. To address this limitation, we introduced a novel self-oriented nanocarrier termed F-GCS@Hb-DIF, designed to synergistically integrate the therapeutic diferuloylmethane (DIF), the polysaccharide fucoidan/glycol chitosan (F-GCS), and phototherapeutic hemoglobin (Hb). F-GCS@Hb-DIF demonstrated the capability to autonomously navigate toward diseased renal sites and directly release drugs into the cytoplasm of target cells following intranasal administration. This self-directed drug delivery system increased the accumulation of Hb and DIF at the target site by around 2–3 times compared to free drugs alone as per biodistribution data. This enhancement allowed F-GCS@Hb-DIF to adopt a synergistic approach in treating the complex pathologies of DKD during the two-week treatment period. This approach entails modulating immunity, promoting renal functional recovery with a tissue-protective effect, and alleviating renal inflammation. These results underscore the promising therapeutic potential of F-GCS@Hb-DIF in managing DKD and other degenerative diseases associated with diabetes.