Structural requirements for intestinal absorption of peptide drugs
Structural requirements for intestinal absorption of peptide drugs
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DOI：
10.1016/0168-3659(96)01352-1
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发表时间：
1996-08-01
影响因子：
10.8
通讯作者：
Borchardt, RT
中科院分区：
文献类型：
--
作者：
Pauletti, GM;Gangwar, S;Borchardt, RT
口服活性多肽药物的理化特性限制了其膜渗透能力，且缺乏抗酶降解的稳定性，限制了其临床发展。因此，成功的口服多肽递送将取决于设计改变这些潜在药物的物理化学特性的策略，而不改变其生物活性，以绕过肠上皮细胞的屏障特性。本文将重点关注肠粘膜的物理和代谢屏障功能，影响其被动扩散和载体介导运输的肽的结构特征，包括外排机制，以及用于防止酶降解肽和增加其在肠粘膜上的渗透性的各种方法。
The clinical development of orally active peptide drugs has been restricted by their unfavorable physicochemical characteristics, which limit their membrane permeation, and their lack of stability against enzymatic degradation. Successful oral delivery of peptides will depend, therefore, on strategies designed to alter the physicochemical properties of these potential drugs, without changing their biological activity, in order to circumvent the barrier properties of the intestinal epithelial cells. This manuscript will focus on the physical and metabolic barrier functions of the intestinal mucosa, the structural features of peptides which influence their passive diffusion and carrier-mediated transport, including efflux mechanisms, and various approaches used to prevent enzymatic degradation of the peptides and increase their permeability across the intestinal mucosa.