Progress in drug delivery to the central nervous system by the prodrug approach.
Progress in drug delivery to the central nervous system by the prodrug approach.
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DOI：
10.3390/molecules13051035
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发表时间：
2008-05-01
期刊：
影响因子：
--
通讯作者：
Vertuani S
中科院分区：
文献类型：
--
作者：
Pavan B;Dalpiaz A;Ciliberti N;Biondi C;Manfredini S;Vertuani S
本文综述了靶向中枢神经系统（CNS）的具体策略。全身给药的药物可以通过跨越两个生理屏障之一到达大脑，这两个生理屏障抵抗大多数分子从血液到CNS的自由扩散：内皮血脑屏障或上皮血脑脊液屏障。这些组织构成了运输和酶的屏障。设计有效前药的最常见策略依赖于母体药物亲脂性的增加。然而，增加亲脂性而不伴随脑中前药生物转化的速率和选择性的增加将导致失败。在这些方面，考虑脑组织和屏障中存在的酶对于成功的方法至关重要。亲脂性前药的鼻内给药可以是一种有前途的替代非侵入性途径，以改善母体药物的脑靶向，因为快速吸收和药物作用的快速起效。载体介导的药物和前药跨上皮和内皮屏障的吸收是生物治疗的另一个新趋势。已经在血液和CNS隔室之间的边界组织中鉴定了几种特异性转运蛋白。它们中的一些参与营养物质的主动供应，并已用于探索具有改善脑递送的前药方法。CNS摄取适当设计的前药通过这些转运蛋白的可行性进行了详细描述。
This review describes specific strategies for targeting to the central nervous system (CNS). Systemically administered drugs can reach the brain by crossing one of two physiological barriers resistant to free diffusion of most molecules from blood to CNS: the endothelial blood-brain barrier or the epithelial blood-cerebrospinal fluid barrier. These tissues constitute both transport and enzymatic barriers. The most common strategy for designing effective prodrugs relies on the increase of parent drug lipophilicity. However, increasing lipophilicity without a concomitant increase in rate and selectivity of prodrug bioconversion in the brain will result in failure. In these regards, consideration of the enzymes present in brain tissue and in the barriers is essential for a successful approach. Nasal administration of lipophilic prodrugs can be a promising alternative non-invasive route to improve brain targeting of the parent drugs due to fast absorption and rapid onset of drug action. The carrier-mediated absorption of drugs and prodrugs across epithelial and endothelial barriers is emerging as another novel trend in biotherapeutics. Several specific transporters have been identified in boundary tissues between blood and CNS compartments. Some of them are involved in the active supply of nutrients and have been used to explore prodrug approaches with improved brain delivery. The feasibility of CNS uptake of appropriately designed prodrugs via these transporters is described in detail.
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DOI：
10.1124/jpet.104.069393
发表时间：
2004-10-01
影响因子：
3.5
作者：
Elmagbari, NO;Egleton, RD;Bilsky, EJ
通讯作者：
Bilsky, EJ
影响因子：
7.3
作者：
Bilsky, EJ;Egleton, RD;Polt, R
通讯作者：
Polt, R
影响因子：
7.3
作者：
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通讯作者：
Prokai, L
DOI：
10.1111/j.1527-3458.2007.00014.x
发表时间：
2007-06-01
期刊：
CNS DRUG REVIEWS
影响因子：
--
作者：
Dvir, Eran;Elman, Anat;Friedman, Jonathan E.
通讯作者：
Friedman, Jonathan E.
影响因子：
5.8
作者：
Dalpiaz, A;Pavan, B;Manfredini, S
通讯作者：
Manfredini, S