| objective: This project focuses on loading bevacizumab to PECEhydrogel, to build bevacizumab PECE hydrogel slow-release system, which isused in intracameral injection for rabbit eyes after filtration operation. Theproject also evaluates the biocompatibility, biodegradability of PECE hydrogelin the eye tissue, which can make bevacizumab slowly release from PECEhydrogel slow-release system to achieve stable long-term slow release drugs,maintain anterior chamber effective drug concentration, extend the filteringbleb survival time, maintain normal form of filtering bleb and reduce thepostoperative intraocular pressure (IOP), promote filtration postoperativewound healing and inhibit scarring formation in rabbit eyes after filtrationoperation and formation of new blood vessels. Methods: prepare PECEhydrogel with a concentration of15%; let it automatically load bevacizumabinto PECE hydrogel to construct sustained release system and then performanimal experiments.24New Zealand white rabbits were randomly divided intofour groups: one group for filtration surgery group+BSS injection; one groupfor filtration surgery+injection of bevacizumab into anterior chamber; onegroup for filtration surgery+injection of PECE hydrogel into anterior chamber;The last group for filtration surgery+injection of PECE hydrogel loading ofbeacizumab into anterior chamber. Before the operation and On the1st,3rd,7th,14th,21st,28th day after the operation, measure the IOP of rabbit eyes; use slit lamp and microscope to clinically observe the conjunctival congestion andcorneal edema of rabbit eyes and then make analysis; Observe degradation timeof PECE hydrogel in anterior chamber of rabbit eye tissue and the reaction ofPECE hydrogel caused in rabbit eye ball; Record the survival time of filteringbleb and also observe its morphology, and kill animals on the28th day after theoperation, doubly stain the rabbit corneal endothelial cells with trypan blue andalizarin red to check the injury of corneal endothelial; The filtering blebregional was dyed by HE staining, Massion staining and Immunohistochemistry,then The filter corridor scar area was analyzed by Histopathological analysis.Results: PECE hydrogel injected into the rabbit anterior chamber wascompletely absorbed in3weeks. No rabbit eye inflammation and eliminationreaction are clinically observed by slit-lamp. Measure the IOP of four groups ofrabbit in different time. It is found that PECE hydrogel injected into anteriorchamber do not elevate intraocular pressure significantly. Compared with othergroups, The last group injectied of PECE hydrogel loading of beacizumab intoanterior chamber decreased intraocular pressure significantly. Filtering blebmorphology in operation area suggest the functions of filtering bleb and filtercorridor are good. Survival time of filtering bleb is much longer than the otherthree groups. The28th day after the operation, Trypan blue-alizarin red doublestaining on rabbit corneal endothelial cells suggests a normal cornealendothelial cell shape and fine color, which do not have significant difference(P>0.05) compared to the group filtration surgery group only. This indicates that PECE hydrogel injected into prompt anterior has no damage to theendothelial cells. Histologic analysis showed that PECE hydrogel did not causeinflammation，also showed that bevacizumab PECE hydrogel delivery systemcan keep the morphological structure of filtering bleb and filter aisle after theoperation, restrain angiogenesis in surgery area, and significantly reduce theαactin (α-SMA) expression and collagen deposition.And it also inhibits thesurgical wound filter aisle scar tissue formation. Conclusion: Bevacizumab canslowly be released from PECE hydrogel controlled release system, other drugscan also be released in a smooth, efficient and durable way in the organism.And PECE hydrogel injected in the anterior chamber damage to normal tissues,completely absorbed in the agreed upon period of time, indicate that PECEhydrogel have good biocompatibility and biodegradability. Bevacizumab canreduce the vascular endothelial growth factor (VEGF) levels in the aqueoushumor after rabbit eyes filtration operation, extend the survival time of filteringbleb and suppress the collagen deposition in scar area of filter corridor andforming of new blood vessels. Bevacizumab PECF hydrogel can maintainmorphological structure of filtering bleb and filtering corridor after filtration inrabbit eyes. Bevacizumab self-assembly PECE hydrogel applied in rabbit eyesfiltration surgery not only can avoid frequent injection of anti-metabolites inanterior chamber and surgery area, which significantly reduce the irritant effectof drug to normal eye tissue around but also can control the filtrationpostoperative intraocular pressure as well as inhibit scar formation after filtration postoperative. |
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