Vitamin D-binding protein-loaded PLGA nanoparticles suppress Alzheimer's disease-related pathology in 5XFAD mice

Seong Gak Jeon; Moon-Yong Cha; Jin-Il Kim; Tae Woong Hwang; Kyoung Ah Kim; Tae Hyoung Kim; Ki Chang Song; Jwa-Jin Kim; Minho Moon

doi:10.1016/j.nano.2019.02.004

Vitamin D-binding protein-loaded PLGA nanoparticles suppress Alzheimer's disease-related pathology in 5XFAD mice

Nanomedicine. 2019 Apr:17:297-307. doi: 10.1016/j.nano.2019.02.004. Epub 2019 Feb 19.

Authors

Seong Gak Jeon¹, Moon-Yong Cha², Jin-Il Kim³, Tae Woong Hwang⁴, Kyoung Ah Kim¹, Tae Hyoung Kim⁵, Ki Chang Song⁵, Jwa-Jin Kim⁶, Minho Moon⁷

Affiliations

¹ Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea.
² Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
³ Department of Nursing, College of Nursing, Jeju National University, Jeju-si, Republic of Korea.
⁴ Department of Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
⁵ Department of Biomedical Materials, Konyang University, Daejeon, Republic of Korea.
⁶ Department of Biomedical Science, Jungwon University, Goesan-gun, Chungbuk, Republic of Korea; Department of Nephrology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea. Electronic address: kjj1021@naver.com.
⁷ Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea. Electronic address: hominmoon@konyang.ac.kr.

PMID: 30794963
DOI: 10.1016/j.nano.2019.02.004

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.

Keywords: 5XFAD mice; Alzheimer's disease; Amyloid beta; Neuronal loss; PLGA; Vitamin-D binding protein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / drug therapy*
Alzheimer Disease / metabolism
Alzheimer Disease / pathology
Amyloid beta-Peptides / metabolism
Animals
Drug Carriers / chemistry*
Male
Mice
Mice, Transgenic
Nanoparticles / chemistry
Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
Protein Aggregation, Pathological / drug therapy
Protein Aggregation, Pathological / metabolism
Protein Aggregation, Pathological / pathology
Vitamin D-Binding Protein / administration & dosage*
Vitamin D-Binding Protein / therapeutic use

Substances

Amyloid beta-Peptides
Drug Carriers
Vitamin D-Binding Protein
Polylactic Acid-Polyglycolic Acid Copolymer