Biocompatibility evaluation of crosslinked chitosan hydrogels after subcutaneous and intraperitoneal implantation in the rat.
The aim of the present study was to evaluate the toxicity of biodegradable hydrogels in the rat with a future aim of utilizing this hydrogel as a vehicle for brachytherapy delivery in cancer patients. Two types of chitosan hydrogels: fast degrading and slow degrading; were prepared and surgically implanted in rats. The adjacent tissue response to the gels after subcutaneous and intraperitoneal implantation was examined histologically and found to be identical to typical foreign body response and was milder than the response to absorbable surgical sutures (Vicril). Neither tissue damage nor gel fragments could be detected in distant organs (brain, heart, lungs, liver, spleen, kidney, and sternal bone marrow) after implantation of the hydrogels. The degradation mechanism of the gels was studied in vivo, and it was deduced that an oxidative process degraded the chitosan. Loading the hydrogels with a radioisotope (131I-norcholesterol) caused a severe tissue response and necrosis in adjacent tissues only at a distance of several microns. It is concluded that crosslinked chitosan implants could serve as alternative, biocompatible, and safe biodegradable devices for radioisotope delivery in brachytherapy for cancer.
Azab
Abdel Kareem
AK
Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
Doviner
Victoria
V
Orkin
Boris
B
Kleinstern
Jackie
J
Srebnik
Morris
M
Nissan
Aviram
A
Rubinstein
Abraham
A
D015071:19-Iodocholesterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005549:Foreign-Body Reaction; D020100:Hydrogels / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007249:Inflammation; D008422:Materials Testing; D009928:Organ Specificity / Q000187:drug effects; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019919:Prosthesis Implantation; D051381:Rats; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D001672:Biocompatible Materials; D015415:Biomarkers; D003432:Cross-Linking Reagents; D020100:Hydrogels; C023033:I-norcholesterol; D015071:19-Iodocholesterol; D048271:Chitosan