CROSSLINKED CHITOSAN IMPLANTS AS POTENTIAL DEGRADABLE DEVICES FOR BRACHYTHERAPY: IN VITRO AND IN VIVO ANALYSIS

Boris Orkin1, Abdel Kareem Azab2, Aviram Nissan3, Martine Klein1,

Morris Srebnik2, Abraham Rubinstein2

1 Hadassah University Medical Center, Ein Kerem, Jerusalem, Israel

2 The Hebrew University of Jerusalem, School of Pharmacy, Jerusalem, Israel

3    Department of Surgery, Hadassah University Medical Center, Mount Scopus, Jerusalem, Israel

 

Compared with conventional external beam radiation, brachytherapy offers a superior therapeutic regimen. However, some major constraints are associated with its implementation, including the need for 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. It is concluded that hydrogels made of crosslinked Ct are potential novel, degradable devices for brachytherapy.

 

The study was supported by a research grant # 596/02-1 from the Israeli Science Foundation.

 

 

 

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