Study On The Effect Of Stress On The Degradation And Drug Release Characteristics Of BFGF Controlled Release Microspheres

Objective: To explore the possible effects of compressive stress and shear force on the degradation and drug release characteristics of bFGF controlled release microspheres (Ms). The characteristic of Ms in the joint fluid was also initially explored through the experiment of biodegradation and drug release in vitro and in the knee joints of rabbits,and to investigate whether stress in the joint fluid is a possible influential machanism for biodegradation of Ms, in order to make an experimental base for the future clinical practice in the treatment of the injured joint cartilage.Method: To elaborate bFGF-PLGA Microspheres(PLGA-Ms) by multiple emulsion encapsulative method and to prepare the freeze-drying powder for using. With PBS solution to be used as medium, the effect of continuous compressive stress (0.35Mpa和4.0Mpa) on the degradation and drug release velocity of bFGF—PLGA-Ms with initial molecular weight as 1.2><105, was investigated in detail by the self-made compressive stress-providing instruments. The effect of shear stress was also initially explored by the self-made liquid shear stress-providing instruments. An animal model were used to inject bFGF Ms into the knee joint cavity of rabbit, joint movements of the control group were limited by plaster cast, and the experimental groups were free to move in cages or on the ground. Cmpare the difference of biodegradation and drug release in vitro and in vivo, and in joint fluid of animal groups with different degree of joint activity.Result: The morphology and the particle size distribution of the bFGF—PLGA Mis were even and good under compressive stress, without Rupture. Under continuous loadings of 0.35Mpa compressive stress and shear force only in liquid, the trend of molecular (Mw) loss, mass loss, and drug release in vitro of PLGA of bFGF Ms was consistent of the experimental group and the control group, with all indexes bearing no significant difference. The results revealed that the degradation velocities of PLGA-Ms under continuous loadings of 4.0Mpa compressive stress were obviously quicker than those of without stress, and the effect was ever more obvious under whirling state. The trend of biodegradation and drug release of bFGF Ms in the joint fluid was consistent with that in vitro, however, the former was greater in velocity after 4 days, and there were remarkable differences among all the indexes. With the increasement of joint activity, the molecular (Mw) loss, the transformation of Ms shape were quickened, and the time of effective durg release in joint fluid was shortened.Conclusion: bFGF controlled release microspheres in the joint cavity could maintain stable on the compressive stress between joint surfaces. The contact pressure between joint cartilage will speedup the process of degradation and drug release, but the intraarticular pressure has no such effect. The shear force in liguid by the movement of joint has little effect on the degradation and drug release characteristics of bFGF controlled release microspheres, but whirling offect will promote the procrss obviously.bFGF Ms had a evidently greater velocity of biodegradation and drug release in the joint fluid than that in vitro, the velocity of biodegradation and drug release of bFGF Ms in joint fluid would be quickened with the increasement of joint activity.