可降解药物控释系统的药物扩散系数表征

Diffusion coefficient expression of degradable controlled drug delivery system

为实现药物的长期稳定释放并提高药物利用率,提出了一种以聚乳酸-聚羟基乙酸(PLGA)为载药基体的新型植入式药物控释系统。该药物控释系统可埋植在病灶附近进行长期释药,在药物释放结束后药物载体自然降解。为研究该药物控释系统的释药性能,建立其药物释放模型、模拟释药过程是有效方法之一,但在建立药物释放模型过程中,不断降解的PLGA材料特性难以量化。文中提出了一种使用扩散系数来表征PLGA材料的降解溶蚀程度的方法,在37℃下使用生理盐水模拟体液,对50/50、65/35及75/25三种单体比例的PLGA材料进行吸水实验和降解实验,并制备全封装药物控释系统进行了体外释药实验。通过实验结果的对比并基于物质守恒与传递定理,推导了封装药物在PLGA载药基体中释放时扩散系数的分段表达函数。基于该扩散系数表达函数,建立了药物通过该给药系统释放的有限元模型;使用有限元模型模拟药物的释放过程,并将有限元模拟结果与该药物控释系统体外释药实验结果进行了对比。结果表明,药物控释系统累积释药量呈线性变化,有限元模型模拟结果与体外释药实验结果基本吻合,验证了药物在PLGA材料中扩散系数分段表达式及有限元释药模型的正确性。该研究为后期建立药物释放的解析模型提供了一定的理论基础。

To control and curb chronic diseases,the long-term and stable drug release is important.In this paper,the controlled drug delivery system(CDDS)which made by poly(lactic-co-glycolic acid)(PLGA)was proposed.CDDS could be implanted around lesions and released drug continuously,the PLGA drug carrier will be degraded to water and carbon dioxide after loaded drug exhausted.To research the CDDS drug release characteristics,establishment of drug release model is one of effective method.In drug release process however,the features of continuous degradation PLGA were difficult to be quantified,so the diffusion coefficient was used to express the degree of PLGA erosion.Three monomers 50/50,65/35 and 75/25 PLGA absorb water,degradation and drug release in-vitro experiments were carried out at 37℃,normal saline was used to imitate body fluid.On the basis of the above experiments and material transfer theorem,the piecewise function of drug diffusion coefficient in PLGA was deducted.The drug releasing FEM model was established based on the drug diffusion coefficient function,and the drug release process was simulated.The reasonableness of the drug diffusion coefficient function is verified by the results comparison of FEM drug release model and in-vitro drug release experiment.The research provides the theoretical basis for the establishment of drug release model.