Rigorous mathematical modeling techniques for optimal delivery of macromolecules to the brain
Rigorous mathematical modeling techniques for optimal delivery of macromolecules to the brain
复制标题
DOI：
10.1109/tbme.2008.923920
复制
发表时间：
2008-09-01
影响因子：
4.6
通讯作者：
Penn, Richard D.
中科院分区：
文献类型：
--
作者：
Linninger, Andreas A.;Somayaji, Mahadevabharath R.;Penn, Richard D.
中枢神经系统的神经变性疾病或肿瘤的几种治疗方式涉及大分子量药物向脑的侵入性递送。尽管有大量的实验研究记录，但精确的药物靶向人类大脑仍然是一个挑战。本文提出了一种基于第一性原理多孔介质输运的药物给药系统设计方法。所提出的数学框架预测可实现的治疗体积在目标区域作为脑解剖结构和输注导管位置的函数。一个系统的程序，以确定最佳的输注和导管设计参数，最大限度地提高渗透深度和体积的分布将进行讨论。琼脂糖凝胶体模实验和大鼠数据的计算机模拟进行了验证。严格的计算方法将使医生和科学家能够更好地计划治疗药物对中枢神经系统的管理。
Several treatment modalities for neurodegenerative diseases or tumors of the central nervous system involve invasive delivery of large molecular weight drugs to the brain. Despite the ample record of experimental studies, accurate drug targeting for the human brain remains a challenge. This paper proposes a systematic design method of administering drugs to specific locations in the human brain based on first principles transport in porous media. The proposed mathematical framework predicts achievable treatment volumes in target regions as a function of brain anatomy and infusion catheter position. A systematic procedure to determine the optimal infusion and catheter design parameters that maximize the penetration depth and volumes of distribution will be discussed. The computer simulations are validated with agarose gel phantom experiments and rat data. The rigorous computational approach will allow physicians and scientists to better plan the administration of therapeutic drugs to the central nervous system.