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제주대학교 간호대학

Nanomed.-Nanotechnol. Biol. Med., Apr 2019, 17 S1549-9634(19)30035-8 | https://doi.org/10.1016/j.nano.2019.02.004 Vitamin D-binding protein-loaded PLGA nanoparticles suppress Alzheimer's disease-related pathology in 5XFAD mice

Seong Gak Jeon^{a 1}, Moon-Yong Cha ^{b 1}, Jin-il Kim ^{c 1}, Tae Woong Hwang ^d, Kyoung Ah Kim ^a, Tae Hyoung Kim ^e, Ki Chang Song ^e, Jwa-Jin Kim^{f g *}, Minho Moon^{a *}

^aDepartment of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea
^bDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
^cDepartment of Nursing, College of Nursing, Jeju National University, Jeju-si, Republic of Korea
^dDepartment of Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
^eDepartment of Biomedical Materials, Konyang University, Daejeon, Republic of Korea
^fDepartment of Biomedical Science, Jungwon University, Goesan-gun, Chungbuk, Republic of Korea
^gDepartment of Nephrology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea

¹These authors contributed equally

^*Corresponding authors: correspondence to Jwa-Jin Kim or Minho Moon

Abstract

The aggregation and accumulation of amyloid beta (Aβ) peptide is believed to be the primary cause of Alzheimer's disease (AD) pathogenesis. Vitamin D-binding protein (DBP) can attenuate Aβ aggregation and accumulation. A biocompatible polymer poly (_D,L-lactic acid-co-glycolic acid) (PLGA) can be loaded with therapeutic agents and control the rate of their release. In the present study, a PLGA-based drug delivery system was used to examine the therapeutic effects of DBP-PLGA nanoparticles in Aβ-overexpressing (5XFAD) mice. DBP was loaded into PLGA nanoparticles and the characteristics of the DBP-PLGA nanoparticles were analyzed. Using a thioflavin-T assay, we observed that DBP-PLGA nanoparticles significantly inhibited Aβ aggregation in vitro. In addition, we found that intravenous injection of DBP-PLGA nanoparticles significantly attenuated the Aβ accumulation, neuroinflammation, neuronal loss and cognitive dysfunction in the 5XFAD mice. Collectively, our results suggest that DBP-PLGA nanoparticles could be a promising therapeutic candidate for the treatment of AD.

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