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 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.
Keywords: Diabetic kidney disease; Diferuloylmethane; Hemoglobin; Intranasal delivery; Polysaccharide.
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