title: Crosslinked chitosan implants as potential degradable devices for brachytherapy: in vitro and in vivo analysis.
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 (131)I-norcholesterol ((131)I-NC) into the SDG altered the degradation kinetics of the gel as reflected by the release kinetics of the radioactive marker. Eighty percent of (131)I-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.
authors.affiliation: Department of Pharmaceutics, The Hebrew University of Jerusalem, School of Pharmacy, P.O. Box 12065, Jerusalem 91120, Israel.
authors.forename: Abdel Kareem
authors.initials: AK
authors.lastname: Azab
authors.forename: Boris
authors.initials: B
authors.lastname: Orkin
authors.forename: Victoria
authors.initials: V
authors.lastname: Doviner
authors.forename: Aviram
authors.initials: A
authors.lastname: Nissan
authors.forename: Martine
authors.initials: M
authors.lastname: Klein
authors.forename: Morris
authors.initials: M
authors.lastname: Srebnik
authors.forename: Abraham
authors.initials: A
authors.lastname: Rubinstein
mesh_terms: D015071:19-Iodocholesterol / Q000031:analogs & derivatives; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage; D001918:Brachytherapy / Q000379:methods*; D048271:Chitosan; D003432:Cross-Linking Reagents; D004343:Drug Implants; D005976:Glutaral; D020100:Hydrogels; D007457:Iodine Radioisotopes; D051381:Rats
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004343:Drug Implants; D020100:Hydrogels; C023033:I-norcholesterol; D007457:Iodine Radioisotopes; D015071:19-Iodocholesterol; D048271:Chitosan; D005976:Glutaral