Self-assembled hyaluronic acid nanoparticles: Implications as a nanomedicine for treatment of type 2 diabetes

Jun Gi Rho; Hwa Seung Han; Ji Hye Han; Hansang Lee; Van Quy Nguyen; Wang Hee Lee; Seunglee Kwon; Sungeun Heo; Juhwan Yoon; Han Ho Shin; Eun young Lee; Hoin Kang; Siyoung Yang; Eun Kyung Lee; Jae Hyung Park; Wook Kim

doi:10.1016/j.jconrel.2018.04.006

Self-assembled hyaluronic acid nanoparticles: Implications as a nanomedicine for treatment of type 2 diabetes

Jun Gi Rho
, Hwa Seung Han
, Ji Hye Han
, Hansang Lee
, Van Quy Nguyen
, Wang Hee Lee
, Seunglee Kwon
, Sungeun Heo
, Juhwan Yoon
, Han Ho Shin
, Eun young Lee
, Hoin Kang
, Siyoung Yang
, Eun Kyung Lee
, Jae Hyung Park
, Wook Kim

Department of Chemical Engineering

Ajou University
Sungkyunkwan University
The Catholic University of Korea

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	89-98
Number of pages	10
Journal	Journal of Controlled Release
Volume	279
DOIs	https://doi.org/10.1016/j.jconrel.2018.04.006
State	Published - 10 Jun 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Hyaluronic acid
Inflammation
Insulin resistance
Nanomedicine
Self-assembled nanoparticles
Type 2 diabetes

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10.1016/j.jconrel.2018.04.006

Cite this

Rho, J. G., Han, H. S., Han, J. H., Lee, H., Nguyen, V. Q., Lee, W. H., Kwon, S., Heo, S., Yoon, J., Shin, H. H., Lee, E. Y., Kang, H., Yang, S., Lee, E. K., Park, J. H., & Kim, W. (2018). Self-assembled hyaluronic acid nanoparticles: Implications as a nanomedicine for treatment of type 2 diabetes. Journal of Controlled Release, 279, 89-98. https://doi.org/10.1016/j.jconrel.2018.04.006

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title = "Self-assembled hyaluronic acid nanoparticles: Implications as a nanomedicine for treatment of type 2 diabetes",

abstract = "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.",

keywords = "Hyaluronic acid, Inflammation, Insulin resistance, Nanomedicine, Self-assembled nanoparticles, Type 2 diabetes",

author = "Rho, \{Jun Gi\} and Han, \{Hwa Seung\} and Han, \{Ji Hye\} and Hansang Lee and Nguyen, \{Van Quy\} and Lee, \{Wang Hee\} and Seunglee Kwon and Sungeun Heo and Juhwan Yoon and Shin, \{Han Ho\} and Lee, \{Eun young\} and Hoin Kang and Siyoung Yang and Lee, \{Eun Kyung\} and Park, \{Jae Hyung\} and Wook Kim",

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doi = "10.1016/j.jconrel.2018.04.006",

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T1 - Self-assembled hyaluronic acid nanoparticles

T2 - Implications as a nanomedicine for treatment of type 2 diabetes

AU - Rho, Jun Gi

AU - Han, Hwa Seung

AU - Han, Ji Hye

AU - Lee, Hansang

AU - Nguyen, Van Quy

AU - Lee, Wang Hee

AU - Kwon, Seunglee

AU - Heo, Sungeun

AU - Yoon, Juhwan

AU - Shin, Han Ho

AU - Lee, Eun young

AU - Kang, Hoin

AU - Yang, Siyoung

AU - Lee, Eun Kyung

AU - Park, Jae Hyung

AU - Kim, Wook

PY - 2018/6/10

Y1 - 2018/6/10

N2 - 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.

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.

KW - Hyaluronic acid

KW - Inflammation

KW - Insulin resistance

KW - Nanomedicine

KW - Self-assembled nanoparticles

KW - Type 2 diabetes

UR - https://www.scopus.com/pages/publications/85045741276

U2 - 10.1016/j.jconrel.2018.04.006

DO - 10.1016/j.jconrel.2018.04.006

M3 - Article

C2 - 29649530

AN - SCOPUS:85045741276

SN - 0168-3659

VL - 279

SP - 89

EP - 98

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -

Self-assembled hyaluronic acid nanoparticles: Implications as a nanomedicine for treatment of type 2 diabetes

Abstract

UN SDGs

Keywords

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