Background The anti-proliferative effect of matrine has been demonstrated and its relevance to prevention and treatment of proliferative retinovitreopathy is concerned.Howeverthe intravitreous injection of free-matrine reiteratively may raise the risk of ocular infection.ObjectiveThe goal of the present study is to investigate the sustained releasing ability and safety of matrine polyactic acid microsphere(MAT-PLA-MSintravitreal injection.MethodsMAT-PLA-MS was prepared by Hebei Medical University and examined under the transmission electron microscope.The release of MAT-PLA-MS was monitored by ultraviolet spectrophotometry.Free-matrine with the dose of 1,2,4mg was intravitreally injected respectively in 12 eyes of New Zealand albino rabbits in free-matrine group and MAT-PLA-MS with matrine(2,4,6mg respectively was administered in 16 eyes separately in matrine microsphere group.The blank microsphere was injected in 6 right eyes as blank control group and normal saline solution was injected in 6 fellow eyes as control group.The retinal function change was evaluated by electroretinogram(ERG),and the morphological and histological change of retina following drug injection were assessed under the slit lamp biomicroscope,indirect ophthalmoscope,light microscope and transmission electron microscope.The decomposed process of MAT-PLA-MS in vitreous was recorded with ocular anterior segment and fundus color camera.Results MAT-PLA-MS containing matrine showed the spherical shape with the mean diameter of 2.28±47μm under the transmission electron microscope and the drug-loading rate 6.17% and drug-release rate 87.93% in vitro for 672 hours,presenting the controllable release characteristics.After implantation into the vitreous,the MAT-PLA-MS containing matrine decomposed gradually with the prolong of time.The b amplitudes of ERG maximum response were significantly declined in 4mg free-matrine injection group in comparison with before injection in various time points(P<0.01).However,no considerably differences were found in MAT-PLA-MS with matrine groups and control groups in various time points following the intravitreal injection(P>0.05).No obvious abnormal was seen under the slim lamp and ophthalmoscope through the study period.The changes of retinal ultrastructure were found from 1 through 28 days after injection of 4mg free-matrine,and slight retinal structural damage was seen from 7 through 28 days after injection of 6mg MAT-PLA-MS containing matrine.ConclusionThese results suggest that MAT-PLA-MS possesses good sustained release feature.MAT-PLA-MS containing matrine has less toxicity to retina than free-matrine after intravitreal injection.MAT-PLA-MS is an excellent drug delivery system.