University of Colorado at Boulder, Department of Chemical and Biological Engineering, 424 UCB, Boulder, CO 80309, USA.
Expert Opin Drug Deliv. 2010 Mar;7(3):285-93. doi: 10.1517/17425240903540205.
Therapeutic proteins and DNA constructs offer promise for the treatment of central nervous system disorders, yet significant biological barriers limit the ability of these molecules to reach the central nervous system from the bloodstream. Direct administrations to the cerebrospinal fluid (intrathecal administration) comprise an emerging field to facilitate the efficient delivery of these biological macromolecules to central nervous system tissues.
Previous reports from 1990 to the present time describing the interactions and turnover of the cerebrospinal fluid within the intrathecal space, characterizations of the effects that therapeutic proteins and DNA have shown after intrathecal delivery through a lumbar route, and reports of emerging technologies to address the limitations of intrathecally administered macromolecules are reviewed.
This review provides an overview of the limitations that must be overcome for intrathecally administered biological macromolecules and the recent advances and promising approaches for surmounting these limitations.
Emerging approaches that stabilize and sustain the delivery of intrathecally administered biological macromolecules may enhance substantially the clinical relevance of promising therapeutic proteins and DNA constructs for the treatment of various central nervous system disorders.
治疗性蛋白和 DNA 构建体为治疗中枢神经系统疾病提供了希望，但这些分子从血液到达中枢神经系统的能力受到显著的生物学屏障限制。直接向脑脊液（鞘内给药）给药构成了一个新兴领域，以促进这些生物大分子向中枢神经系统组织的有效传递。
描述了从 1990 年到现在的先前报告，这些报告描述了脑脊液在鞘内空间内的相互作用和周转率，以及治疗性蛋白和 DNA 在通过腰部途径鞘内给药后表现出的影响的特征，以及新兴技术的报告，以解决鞘内给予大分子的局限性。
本综述提供了对鞘内给予的生物大分子必须克服的局限性的概述，以及最近克服这些局限性的进展和有前途的方法。
新兴的方法可以稳定和维持鞘内给予的生物大分子的输送，这可能会大大增强有前途的治疗性蛋白和 DNA 构建体在治疗各种中枢神经系统疾病中的临床相关性。
