PMID- 29649530
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20190722
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 279
DP  - 2018 Jun 10
TI  - Self-assembled hyaluronic acid nanoparticles: Implications as a nanomedicine for 
      treatment of type 2 diabetes.
PG  - 89-98
LID - S0168-3659(18)30180-9 [pii]
LID - 10.1016/j.jconrel.2018.04.006 [doi]
AB  - Self-assembled hyaluronic acid nanoparticles (HA-NPs) have been extensively 
      investigated for biomedical and pharmaceutical applications owing to their 
      biocompatibility and receptor-binding properties. Here, we report that an empty 
      HA-NP itself not bearing any drug has therapeutic effects on adipose tissue 
      inflammation and insulin resistance. HA-NPs inhibited not only the 
      receptor-mediated internalization of low-molecular-weight (LMW) free HA but also 
      LMW free HA-induced pro-inflammatory gene expression in mouse primary bone 
      marrow-derived macrophages (BMDMs) isolated from wild-type mice, but not in 
      CD44-null (CD44-/-) BMDMs. An in vivo biodistribution study showed the 
      distribution of HA-NPs and their co-localization with CD44 in adipose tissues 
      including epididymal white adipose tissues (eWATs), but these were rarely 
      observed in the eWATs of CD44-/- mice. In addition, CD44 expression and HA-NP 
      accumulation in the eWATs were increased in mice with diet-induced obesity (DIO) 
      compared to lean mice. Interestingly, treatment with HA-NPs in DIO mice 
      suppressed adipose tissue inflammation as indicated by reduced macrophage 
      content, the production of proinflammatory cytokines and NLRP3 inflammasome 
      activity in eWATs, leading to improved insulin sensitivity and normalized blood 
      glucose levels. Collectively, these results suggest that an empty HA-NP itself 
      can be a therapeutic agent for the treatment of type 2 diabetes.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Rho, Jun Gi
AU  - Rho JG
AD  - Department of Molecular Science & Technology, Ajou University, Suwon 16499, 
      Republic of Korea.
FAU - Han, Hwa Seung
AU  - Han HS
AD  - School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of 
      Korea.
FAU - Han, Ji Hye
AU  - Han JH
AD  - Department of Molecular Science & Technology, Ajou University, Suwon 16499, 
      Republic of Korea.
FAU - Lee, Hansang
AU  - Lee H
AD  - School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of 
      Korea.
FAU - Nguyen, Van Quy
AU  - Nguyen VQ
AD  - School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of 
      Korea.
FAU - Lee, Wang Hee
AU  - Lee WH
AD  - Department of Molecular Science & Technology, Ajou University, Suwon 16499, 
      Republic of Korea.
FAU - Kwon, Seunglee
AU  - Kwon S
AD  - School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of 
      Korea.
FAU - Heo, Sungeun
AU  - Heo S
AD  - Department of Molecular Science & Technology, Ajou University, Suwon 16499, 
      Republic of Korea.
FAU - Yoon, Juhwan
AU  - Yoon J
AD  - Department of Molecular Science & Technology, Ajou University, Suwon 16499, 
      Republic of Korea.
FAU - Shin, Han Ho
AU  - Shin HH
AD  - Department of Molecular Science & Technology, Ajou University, Suwon 16499, 
      Republic of Korea.
FAU - Lee, Eun-Young
AU  - Lee EY
AD  - Department of Molecular Science & Technology, Ajou University, Suwon 16499, 
      Republic of Korea.
FAU - Kang, Hoin
AU  - Kang H
AD  - Department of Biochemistry, College of Medicine, The Catholic University of 
      Korea, Seoul 06591, Republic of Korea.
FAU - Yang, Siyoung
AU  - Yang S
AD  - Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, 
      Republic of Korea.
FAU - Lee, Eun Kyung
AU  - Lee EK
AD  - Department of Biochemistry, College of Medicine, The Catholic University of 
      Korea, Seoul 06591, Republic of Korea.
FAU - Park, Jae Hyung
AU  - Park JH
AD  - School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of 
      Korea; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan 
      University, Suwon 16419, Republic of Korea. Electronic address: jhpark1@skku.edu.
FAU - Kim, Wook
AU  - Kim W
AD  - Department of Molecular Science & Technology, Ajou University, Suwon 16499, 
      Republic of Korea. Electronic address: wookkim21@ajou.ac.kr.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180409
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Blood Glucose)
RN  - 0 (Cd44 protein, mouse)
RN  - 0 (Cytokines)
RN  - 0 (Hyaluronan Receptors)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Adipose Tissue/drug effects/pathology
MH  - Animals
MH  - Blood Glucose/drug effects
MH  - Cytokines/metabolism
MH  - Diabetes Mellitus, Type 2/drug therapy/genetics
MH  - Hyaluronan Receptors/genetics
MH  - Hyaluronic Acid/*administration & dosage/pharmacokinetics
MH  - Inflammation/*drug therapy/pathology
MH  - Insulin Resistance
MH  - Macrophages/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Mice, Knockout
MH  - Nanomedicine/methods
MH  - Nanoparticles/*administration & dosage
MH  - Obesity/metabolism
MH  - Tissue Distribution
OTO - NOTNLM
OT  - Hyaluronic acid
OT  - Inflammation
OT  - Insulin resistance
OT  - Nanomedicine
OT  - Self-assembled nanoparticles
OT  - Type 2 diabetes
EDAT- 2018/04/13 06:00
MHDA- 2019/07/23 06:00
CRDT- 2018/04/13 06:00
PHST- 2018/02/22 00:00 [received]
PHST- 2018/03/28 00:00 [revised]
PHST- 2018/04/05 00:00 [accepted]
PHST- 2018/04/13 06:00 [pubmed]
PHST- 2019/07/23 06:00 [medline]
PHST- 2018/04/13 06:00 [entrez]
AID - S0168-3659(18)30180-9 [pii]
AID - 10.1016/j.jconrel.2018.04.006 [doi]
PST - ppublish
SO  - J Control Release. 2018 Jun 10;279:89-98. doi: 10.1016/j.jconrel.2018.04.006. 
      Epub 2018 Apr 9.