A theoretical model of erosion and macromolecular drug release from biodegrading microspheres
A theoretical model of erosion and macromolecular drug release from biodegrading microspheres
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DOI：
10.1021/js9604117
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发表时间：
1997-12-01
影响因子：
3.8
通讯作者：
Edwards, DA
中科院分区：
文献类型：
--
作者：
Batycky, RP;Hanes, J;Edwards, DA
本文提出了一个理论模型，用于预测双乳化法制备的含有亲水性药物（如蛋白质或肽）的球形体积侵蚀微球的总质量、平均分子量和药物释放的时间演变。导出了用于计算可测量的宏观特征（如药物释放或平均分子量）的时间演变的显式解析公式。结果表明，仅通过随机链断裂或端部断裂（或解压缩）的聚合物降解不能解释实验观察到的颗粒质量损失和分子量变化动力学；因此，提出了一个结合随机和末端断裂的组合模型。概述了从腐蚀和释放数据确定微观传输系数（如聚合物降解速率常数或药物扩散系数）的一般方法。这种模式适用于50:50聚D， l -乳酸-羟基乙酸（PLGA）微球包封糖蛋白120 （gp 120）的具体情况，这是一种候选的竞价疫苗，预测允许与平均重量和数平均分子量的实验数据进行比较，以及质量损失和蛋白质释放。其他的比较数据出现在文献中，从可变分子量的聚乳酸微球和聚乳酸微球释放破伤风环。理论与实验结果一致。
A theoretical model is outlined for predicting the time evolution of total mass, mean molecular weight, and drug release for the case of a spherical bulk-eroding microsphere, prepared by a double emulsification procedure and containing a hydrophilic drug, such as a protein dr peptide. Explicit analytical formulae are derived for calculating the time evolution of measurable macroscopic characteristics, such as drug release or mean molecular weight. Microsphere hydration, polymer erosion, and drug release phases are each described, Results indicate that polymer degradation by only random-chain scission or only end scission (or unzipping) cannot explain experimentally observed kinetics of particle mass loss and molecular weight change; thus, a combined model (incorporating both random and end scission) is proposed. a general methodology for determining the microscopic transport coefficients (such as polymer degradation rate constant or drug diffusion coefficient) from erosion and release data is outlined. This paradigm is applied to the specific case of 50:50 poly(D,L-lactic-co-glycolic acid (PLGA) microspheres encapsulating glycoprotein 120 (gp 120), a candidate BIDS vaccine, Predictions permit comparisons with experimental data for mean weight- and number-averaged molecular weights, as well as for mass loss and protein release. Other comparisons are made with data appearing in the literature for release of tetanus toroid from PLA and PLGA microspheres of variable molecular weight. Agreement between theory and experiment is observed.