Applied Biochemistry and Biotechnology

, Volume 169, Issue 1, pp 239–249 | Cite as

Preparation of Hyaluronic Acid Micro-Hydrogel by Biotin–Avidin-Specific Bonding for Doxorubicin-Targeted Delivery



Hyaluronic acid is a naturally ionic polysaccharide with cancer cell selectivity. It is an ideal candidate material for delivery of anticancer agents. In this study, hyaluronic acid (HA) micro-hydrogel loaded with anticancer drugs was prepared by the biotin–avidin system approach. Firstly, carboxyl groups on HA were changed into amino groups with adipic acid dihydrazide (ADH) to graft with biotin by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride named as HA–biotin. When HA–biotin solution mixed with doxorubicin hydrochloride (DOX·HCl) was blended with neutravidin, the micro-hydrogels would be formed with DOX loading. If excess biotin was added into the microgel, it would be disjointed, and DOX will be released quickly. The results of the synthesis procedure were characterized by 1H-NMR and FTIR; ADH and biotin have been demonstrated to graft on the HA molecule. A field emission scanning electron microscope was used to observe morphologies of HA micro-hydrogels. Furthermore, the in vitro DOX release results revealed that the release behaviors can be adjusted by adding biotin. Therefore, the HA micro-hydrogel can deliver anticancer drugs efficiently, and the rate of release can be controlled by biotin-specific bonding with the neutravidin. Consequently, the micro-hydrogel will perform the promising property of switching in the specific site in cancer therapy.


Hyaluronic acid Biotin–avidin Micro-hydrogel Drug delivery DOX 


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Yuan Cui
    • 1
  • Yanhui Li
    • 1
  • Qian Duan
    • 1
  • Toyoji Kakuchi
    • 2
  1. 1.School of Materials Science and EngineeringChangchun University of Science and TechnologyChangchunChina
  2. 2.Division of Biotechnology and Macromolecular Chemistry, Graduate school of EngineeringHokkaido UniversitySapporoJapan

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