Crosslinked chitosan implants as potential degradable devices for brachytherapy: In vitro and in vivo analysis

Abdel Kareem Azab, Boris Orkin, Victoria Doviner, Aviram Nissan, Martine Klein, Morris Srebnik, Abraham Rubinstein

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Compared with conventional external beam radiation, brachytherapy offers a superior therapeutic regimen. However, some major constraints are associated with its implementation, including the need of complicated procedures for device placement and removal. The purpose of this study was to examine whether crosslinked chitosan (Ct) implants could serve as potential biodegradable devices for brachytherapy. Ct was reacted with increasing amounts of glutaraldehyde to obtain hydrogels with different crosslinking densities, which were characterized chemically, thermally and mechanically. The effect of the dialysis medium conditions (ionic strength, osmolarity and pH) on the gel hydration and in vivo degradation was assessed. Two types of implants, slow and fast degrading gel (SDG and FDG, respectively), were prepared and implanted with or without Sudan Black (SB) in the rat. While SDG withstood for over a month, the FDG degraded within two weeks after implantation. The release kinetics of SB from the hydrogels verified their in vivo degradation properties. The incorporation of the radioactive compound 131I-norcholesterol ( 131I-NC) into the SDG altered the degradation kinetics of the gel as reflected by the release kinetics of the radioactive marker. Eighty percent of 131I-NC was released within a month after implantation, after which time, radioactivity was detected in the regional lymph nodes. Histological examination of the tissues surrounding the implants demonstrated negligible tissue response to the implants, when compared to biodegradable surgical sutures. It is concluded that hydrogels made of crosslinked Ct are potential novel, safe, degradable devices for brachytherapy.

Original languageEnglish
Pages (from-to)281-289
Number of pages9
JournalJournal of Controlled Release
Volume111
Issue number3
DOIs
StatePublished - Apr 10 2006
Externally publishedYes

Keywords

  • Brachytherapy
  • Chitosan
  • Degradable implant
  • I-norcholesterol
  • In vivo degradation

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