| Intra brain-tissue biocompatibility is essential for a system for interstitial drug delivery in the brain, we therefore evaluated the biocompatibility in the rat brain of a biodegradable nature high polymer, Chitosan.Thirty-two adult Sprague-Dawley rats were obtained from the experimental animal center of our university with free access to certified rodent chow and city water. The rats were randomly assigned to one of tow groups, each group containing sixteen rats. Medical grade Chitosan was obtained from Shanghai's Boao Biology Science and Technology Limited Corporation (No.000824). The polymer was formulated by compression molding into globes weighing about 16mg ,measuring 2mm in diameter, which were subsequently sterilized under UV light for about 2h. Gel foam (The Jin ling Pharmaceutical Corporation, Nan-jing, China) were subsequently sterilized under UV light for about 2h. The animals were anesthetized intraperitoneally with 1% sodium pentobarbital solution. Unilateral burr holes 3mm in diameter were made at the temporal lobe, 2mm off the coronal suture and 3mm off the sagittal suture without damaging the underlying dura. An avascular region of the cortex was selected and an incision about 3mm deep was made with a No. 15 blade. Once the bleeding subsided, the implants were introduced into the cortical defect. After the introduction of the implant, the dural edges were reapproximated, and the defect of the skull was closed with Bone wax. The animals were examined daily after surgery. Particular attention was given to behavioral changes manifested by decreased alertness, irritability and to neurological deficits manifested by focal motor changes or gait disturbances. The every group were sacrificed sequentially on postoperative days 3,7,14,30. The brains were removed, fixed in 10% phosphate buffered formalin for 10 days and stained with haematoxylin and eosin. A qualitative assessment of the inflammatory reaction in the region of the implants was carried out. The acute or chronic elements of the inflammatory response were described.None of the animals showed any behavioral changes or neurological deficits. Local reaction of surrounding tissues of the transplants was observed with H.E stain after the transplantation at 3,7,14 and 30 days. Chitosan evoked a well-localized inflammatory reaction compatible to that of Gel foam. The course of the inflammatory changes around the implants was divided into three stages: acute, subacute and chronic.Briefly, during the acute phase-characterized by the predominance of neutrophils-the Chitosan polymer induced the more pronounced reaction than by Gel foam. In the subacutephase-characterized by the predominance of lymphocytes -Gel foam was associated with more pronounced response than the Chitosan polymer. In the chronic phase-characterized by maximal degradation of the implants-the localized foreign substance inflammatory reaction evoked by the Chitosan polymer was comparable to that seen in the presence of Gel foam. The count ( 400, per 1/4 field) of the neutrophils around the chitosan by day 7 was 68.75 + 8.14, and around the gelfoam was 33 6.22, respectively (P=0. 001, t=6.98); The count of polymorphonuclear leukocytes was 15.25 3.86 and 7.5 + 2.65, respectively (p=0.019, t=3.311). By day 14 the count of neutrophils arounded the chitosan was 44.50 + 4.44 and compared with control, 25.50 + 3.87 (P=0.001, t=6.454); The count of polymorphonuclear leukocytes was 25.00 + 3.16 and compared with control, 15.00 + 2.58 (P=0.003, t=4.899); The count of epithelioid histiocytes was 7.75 2.22 and 4.3 2.08, respectively (P=0.077, t=2.137). By day 30 the count of neutrophils in chitosan group was 8 1.8; the count in another group was 4.5 1.30 (P=0.230, t=3.130); the count of polymorphonuclear leukocytes was 19 3.56 and 10.25 2.99, respectively (P=0.010 K3.767); the count of epithelioid histiocytes was 7.75 1.71 and 3.0 0.82, respectively (P=0.006, t=5.019).This study suggests that this polymer could be implanted safely in the brain for the interstitial delivery of d...
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