PTMC-F127-PTMC thermosensitive hydrogel as mitomycin C delivery implant for rabbit trabeculactory surgery / 中华实验眼科杂志

ABSTRACT

Background Mitomycin C (MMC) is still irreplaceable until now.While it's current administration method has proved less than effective in the treatment of refractory glaucoma.To construct a MMC sustained release system which can maintain effective concentration and reduce toxicity is important for postoperative scarring regulation after glaucoma filtration surgery.Objective To evaluate the postoperative effect of use PTMC-F127-PTMC thermosensitive hydrogel as a new drug delivery carrier to sustained release MMC in rabbit trabeculactory.Methods Sixty rabbits,aged 10 to 14 weeks,were divided into 5 trabeculectomy groups in accordance with the random number table,including surgery only group,blank PTMC-F127-PTMC group and three sustained groups with 0.1 ml PTMC-F127-PTMC loaded with 0.05,0.10,0.20 g/L MMC injected after surgery.The MMC concentration of anterior chamber aqueous in three sustained release group with 0.1 ml PTMC-F127-PTMC loaded with 0.05,0.1,0.2 g/L MMC injected after surgery were tested by Guangzhou Analysis and Testing Center using high performance liquid chromatograph-mass spectrometer (HPLC-MS).At 3,7 days postoperatively,0.1 ml aqueous humor from 2 random selected rabbits in each group was extracted using 1 ml syringe with 30G needles from corneal limbus.At postoperative 1,3,5,7,10,14,28 days,bleb width and depth were calculated with caliper measurements and height was graded semiquantitatively by slit-lamp examinations,intraocular pressure (IOP) was measured with Tonopen.And corneal endothelial cell densities were examined by corneal endothelial counting before and 28 days after surgery.Sequential sections of the operative region were prepared and stained with hematoxylin and eosin and proliferating cell nuclear antigen (PCNA) after taking off the eyeballs from dead rabbits at 28 days later.Results MMC could be sustained released from PTMC-F127-PTMC hydrogel for more than 20 days.The mean postoperative bleb survival time in trabeculectomy surgery only group,blank hydrogel group and three sustained release groups were (5.3 ± 0.4),(5.5 ± 0.4),(12.2 ± 1.0),(25.1 ± 0.9),(26.7 ± 0.7) days respectively,the difference between each group was significantly (F =123.200,P =0.000).0.05 g/L MMC sustained release group has a better bleb survival time than that of surgery only group and blank hydrogel group (P =0.000).Compared with other groups,0.10 g/L and 0.20 g/L MMC sustained group has the longest bleb survival time (P =0.000),and more obvious IOP downtrending (F=53 010.000,P＜0.01).But the difference between the two groups was not significant.There was no difference in cornea endothelia cells counts between each group and no MMC was detected in aqueous humors.Histopathology test shows that the inflammatory response and fibrosis were lighter in MMC sustained release group,with stronger proliferation inhibition.Conclusions PTMC-F127-PTMC thermosensitive hydrogel can be a new drug delivery carrier to sustained release MMC.Sustain release MMC can extent bleb survival time with low toxicity.