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Pharmaceutical Research

, Volume 31, Issue 9, pp 2453–2462 | Cite as

Local Co-Delivery of Pancreatic Islets and Liposomal Clodronate Using Injectable Hydrogel to Prevent Acute Immune Reactions in a Type 1 Diabetes

  • Muhammad R. Haque
  • Dong Yun Lee
  • Cheol-Hee Ahn
  • Jee-Heon JeongEmail author
  • Youngro ByunEmail author
Research Paper

ABSTRACT

Purpose

The purpose of this study was to investigate the effect of locally delivered pancreatic islet with liposomal clodronate (Clodrosome®) as an immunoprotection agent for the treatment of type 1 diabetes.

Method

The bio-distribution of liposomal clodronate in matrigel was checked by imaging analyzer. To verify the therapeutic efficacy of locally delivered islet with liposomal clodronate using injectable hydrogel, four groups of islet transplanted mice (n = 6 in each group) were prepared: 1) the islet group, 2) the islet-Clodrosome group, 3) the islet-Matrigel group, and 4) the islet-Matrigel-Clodrosome group. Immune cell migration and activation, and pro-inflammatory cytokine secretion was evaluated by immunohistochemistry staining and ELISA assay.

Results

Cy5.5 labeled liposomes remained in the matrigel for over 7 days. The median survival time of transplanted islets (Islet-Matrigel-Clodrosome group) was significantly increased (>60 days), compared to other groups. Locally delivered liposomal clodronate in matrigel effectively inhibited the activation of macrophages, immune cell migration and activation, and pro-inflammatory cytokine secretion from macrophages.

Conclusions

Locally co-delivered pancreatic islets and liposomal clodronate using injectable hydrogel effectively cured type 1 diabetes. Especially, the inhibition of macrophage attack in the early stage after local delivery of islets was very important for the successful long-term survival of delivered islets.

KEY WORDS

pancreatic islets liposomal clodronate injectable hydrogel local delivery macrophage depletion 

ABBREVIATIONS

CD

Cluster of differentiation

ELISA

Enzyme-linked immunosorbent assay

IEQ

Islet equivalent

IL-1β

Interleukin-1 beta

RPMI

Roswell park memorial institute medium

SD

Standard deviation

SEM

Standard error of mean

TNF-α

Tumor necrosis factor-alpha

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

This study was supported by grants from the Converging Research Center Program (grant no. 2012K001398) and Basic Science Research Program (grant no. 2010–0029407) funded through the National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology, and the Korea Health Technology R&D Project (grant no. HI12C1853) of the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Research Institute of Pharmaceutical Science, College of PharmacySeoul National UniversitySeoulRepublic of Korea
  2. 2.Department of Bioengineering, College of Engineering Institute for Bioengineering and Biopharmaceutical ResearchHanyang UniversitySeoulRepublic of Korea
  3. 3.Engineering Research Institute Department of Materials Science and EngineeringSeoul National UniversitySeoulRepublic of Korea
  4. 4.College of PharmacyYeungnam UniversityGyeongsanRepublic of Korea
  5. 5.Department of Molecular Medicine and Biopharmaceutical Sciences Graduate School of Convergence Science and TechnologySeoul National UniversitySeoulRepublic of Korea

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