Action of slow-release drug deliver system with poly lactic acid hydrogels in prevention of tracheal fibroplasia

OBJECTIVE To compare the effect of slow-release mitomycin C(MMC)and dexamethasone sodium phosphate(DSP) with polylactic acid(PLA)hydrogels on prevention of tracheal fibroplasia.METHODS In vitro slow-release study,MMC and DSP mixed with PLA hydrogels was palced in the water bath oscillators,the cumulative concentrations of MMC and DSP were determined by ultraviolet spectrophotometry.In vivo study,the rabbit model of tracheal fibroplasia was made through scratching the tracheal wall.After scuffing the tracheal walls,forty-two rabbits were divided into 7 groups averagely,three MMC groups(0.1、0.2、 0.4 mg),three DSP groups(1、2、3 mg)and one control group.And then the blood drug level of rabbits in 0.4 mg MMC group at different time after operation was determined by mass spectrometry(MS).The blood routine test was done at above-mentioned corresponding time.Four weeks after operation,each animal was killed to get tracheal walls,which were then stained with hematoxylin and eosin(HE),and the thickness of tracheal fibroplasia was calculated.RESULTS In vitro study,PLA hydrogels with 1 mg MMC and 2 mg DSP could release drug over 35 days and 28 days respectively.And in vivo study,these two kinds of PLA hydrogels hadn't degraded completely after 4 weeks.The tracheal wall fibroplasia in control group was thicker than that in both DSP and MMC groups except 0.1 mg MMC group.Among MMC groups,0.4 mg MMC group had the best effect in inhibiting fibroplasia.While in DSP groups,the thickness of fibroplasia had no difference among three groups;and the difference of fibroplasia thickness was not significant between DSP groups and 0.4 mg MMC group.The leukocyte count on the 1st day,7th day and 14th day after operation had no significant difference.CONCLUSION MMC and DSP PLA hydrogels could release drug over 4 weeks either in vitro or in vivo.Both MMC/PLA and DSP/PLA hydrogels could inhibit fibroplasia of the tracheal wall and be used as slow-release administration in prevention of fibroplasia,which provided experimental basis for studying PLGA scaffold slow-delivery system for treating laryngotracheal stenosis in the future.