TY - JOUR
T1 - Crosslinked chitosan implants as potential degradable devices for brachytherapy
T2 - In vitro and in vivo analysis
AU - Azab, Abdel Kareem
AU - Orkin, Boris
AU - Doviner, Victoria
AU - Nissan, Aviram
AU - Klein, Martine
AU - Srebnik, Morris
AU - Rubinstein, Abraham
N1 - Funding Information:
The results reported here are included in the dissertation project of A. K. Azab in partial fulfillment of his Ph.D. degree requirements at The Hebrew University of Jerusalem. The study was supported by a research grant # 596/02-1 from the Israeli Science Foundation. The help of Dr. Jackie Kleinstern in editing the manuscript is acknowledged with pleasure.
PY - 2006/4/10
Y1 - 2006/4/10
N2 - 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.
AB - 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.
KW - Brachytherapy
KW - Chitosan
KW - Degradable implant
KW - I-norcholesterol
KW - In vivo degradation
UR - http://www.scopus.com/inward/record.url?scp=33645302350&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2005.12.014
DO - 10.1016/j.jconrel.2005.12.014
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C2 - 16499987
AN - SCOPUS:33645302350
SN - 0168-3659
VL - 111
SP - 281
EP - 289
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -