title: The Alginate Layer for Improving Doxorubicin Release and Radiolabeling Stability of Chitosan Hydrogels.
abstract: OBJECTIVE
  Chitosan hydrogels (CSH) formed through ionic interaction with an anionic molecule are suitable as a drug carrier and a tissue engineering scaffold. However, the initial burst release of drugs from the CSH due to rapid swelling after immersing in a biofluid limits their wide application as a drug delivery carrier. In this study, alginate layering on the surface of the doxorubicin (Dox)-loaded and I-131-labeled CSH (DI-CSH) was performed. The effect of the alginate layering on drug release behavior and radiolabeling stability was investigated.
  
  
  METHODS
  Chitosan was chemically modified using a chelator for I-131 labeling. After labeling of I-131 and mixing of Dox, the chitosan solution was dropped into tripolyphosphate (TPP) solution using an electrospinning system to prepare spherical microhydrogels. The DI-CSH were immersed into alginate solution for 30 min to form the crosslinking layer on their surface. The formation of alginate layer on the DI-CSH was confirmed by Fourier transform infrared spectroscopy (FT-IR) and zeta potential analysis. In order to investigate the effect of alginate layer, studies of in vitro Dox release from the hydrogels were performed in phosphate buffered in saline (PBS, pH 7.4) at 37 °C for 12 days. The radiolabeling stability of the hydrogels was evaluated using ITLC under different experimental condition (human serum, normal saline, and PBS) at 37 °C for 12 days.
  
  
  RESULTS
  Formatting the alginate-crosslinked layer on the CSH surface did not change the spherical morphology and the mean diameter (150 ± 10 μm). FT-IR spectra and zeta potential values indicate that alginate layer was formed successfully on the surface of the DI-CSH. In in vitro Dox release studies, the total percentage of the released Dox from the DI-CSH for 12 days were 60.9 ± 0.8, 67.3 ± 1.4, and 71.8 ± 2.5 % for 0.25, 0.50, and 1.00 mg Dox used to load into the hydrogels, respectively. On the other hand, after formatting alginate layer, the percentage of the released Dox for 12 days was decreased to 47.6 ± 1.4, 51.1 ± 1.4, and 57.5 ± 1.6 % for 0.25, 0.50, and 1.00 mg Dox used, respectively. The radiolabeling stability of DI-CSH in human serum was improved by alginate layer.
  
  
  CONCLUSIONS
  The formation of alginate layer on the surface of the DI-CSH is useful for improving the drug release behavior and radiolabeling stability.
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Science, Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, Jeonbuk 500-757 Republic of Korea.
authors.forename: Jeong Il
authors.initials: JI
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Engineering, Chonnam National University, Yeosu, Jeonnam 500-757 Republic of Korea.
authors.forename: Chang-Moon
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Science, Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, Jeonbuk 500-757 Republic of Korea.
authors.forename: Hwan-Seok
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Science, Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, Jeonbuk 500-757 Republic of Korea.
authors.forename: Phil-Sun
authors.initials: PS
authors.lastname: Oh
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Science, Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, Jeonbuk 500-757 Republic of Korea.
authors.forename: Hyosook
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Science, Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, Jeonbuk 500-757 Republic of Korea.
authors.forename: Seok Tae
authors.initials: ST
authors.lastname: Lim
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Science, Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, Jeonbuk 500-757 Republic of Korea.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Sohn
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Science, Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, Jeonbuk 500-757 Republic of Korea.
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
keywords: Alginate; Chitosan hydrogels; Doxorubicin release; Electrospinning system; Radiolabeling stability