Fucoidan-based micelles as P-selectin targeted carriers for synergistic treatment of acute kidney injury.

Affiliation

Shu G(1), Lu C(2), Wang Z(3), Du Y(4), Xu X(5), Xu M(2), Zhao Z(2), Chen M(2), Dai Y(6), Weng Q(2), Fang S(2), Fan K(2), Liu D(5), Du Y(7), Ji J(8).
Author information:
(1)Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, School of Medicine, Lishui, Zhejiang, China; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
(2)Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, School of Medicine, Lishui, Zhejiang, China.
(3)First Clinical College of traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China.
(4)Department of Chemistry, Faculty of Science, Tohoku University, Sendai, Japan.
(5)Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
(6)Department of Gastroenterology, The Fourth Affiliated Hospital of Zhejiang University, School of Medicine, YiWu, China.
(7)Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China. Electronic address: [Email]
(8)Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, School of Medicine, Lishui, Zhejiang, China. Electronic address: [Email]

Abstract

Acute kidney injury (AKI) is a life-threatening disease without effective treatment. The utilization of curcumin (Cur) for the treatment of AKI is still facing challenges due to its poor water-solubility and low bioavailability. Herein, kidney-targeted octenyl succinic anhydride-grafted fucoidan loaded with Cur (OSA-Fucoidan/Cur) was fabricated for synergistic treatment of AKI. It was found that OSA-Fucoidan/Cur micelles had a sustained drug release behavior and excellent physicochemical stability. Cellular uptake studies demonstrated that the specific binding between fucoidan and P-selectin overexpressed on H2O2-stimulated HUVECs contributed to the higher internalization of OSA-Fucoidan/Cur micelles by the cells. In addition, OSA-Fucoidan micelles exhibited an ideal kidney-targeted characteristic in lipopolysaccharide (LPS)-induced AKI mice. In vivo studies showed that the combination of Cur and OSA-Fucoidan endowed the OSA-Fucoidan/Cur micelles with synergistically anti-inflammatory and antioxidant abilities, thereby largely enhancing the therapeutic efficacy of AKI. Therefore, OSA-Fucoidan/Cur micelles may represent a potential kidney-targeted nanomedicine for effective treatment of AKI.