Fatty acids as therapeutic auxiliaries for oral and parenteral formulations.
Fatty acids as therapeutic auxiliaries for oral and parenteral formulations.
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DOI：
10.1016/j.addr.2012.07.012
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发表时间：
2013-10
影响因子：
16.1
通讯作者：
Cho, Moo J.
中科院分区：
文献类型：
--
作者：
Hackett, Michael J.;Zaro, Jennica L.;Shen, Wei-Chiang;Guley, Patrick C.;Cho, Moo J.
关键词：
由于吸收、分布、代谢和排泄问题，许多药物的治疗活性下降。药物与脂肪酸的共制剂或共价连接已经证明了通过改善肠渗透性、减缓清除和结合血清蛋白以用于选择性组织摄取和代谢来克服这些问题的一些能力。对于口服给药的药物，尽管可用性水平较低，但肠腔中脂肪酸和甘油三酯的存在可促进小亲水分子的肠摄取。小的亲脂性药物或酰化的亲水性药物也显示增加的淋巴摄取和增强的被动扩散摄取。小蛋白质和大蛋白质或肽的脂肪酸缀合物在肠胃外施用时表现出延长的血浆半衰期、位点特异性递送和持续释放。这些改善最有可能是由于与脂质结合血清蛋白，即白蛋白，LDL和HDL的关联。这些分子间的相互作用，虽然没有完全表征，但可以提供使用内源性载体系统来改善治疗结果的能力。
Many drugs have decreased therapeutic activity due to issues with absorption, distribution, metabolism and excretion. The co-formulation or covalent attachment of drugs with fatty acids has demonstrated some capacity to overcome these issues by improving intestinal permeability, slowing clearance and binding serum proteins for selective tissue uptake and metabolism. For orally administered drugs, albeit at low level of availability, the presence of fatty acids and triglycerides in the intestinal lumen may promote intestinal uptake of small hydrophilic molecules. Small lipophilic drugs or acylated hydrophilic drugs also show increased lymphatic uptake and enhanced passive diffusional uptake. Fatty acid conjugation of small and large proteins or peptides have exhibited protracted plasma half-lives, site-specific delivery and sustained release upon parenteral administration. These improvements are most likely due to associations with lipid-binding serum proteins, namely albumin, LDL and HDL. These molecular interactions, although not fully characterized, could provide the ability of using the endogenous carrier systems for improving therapeutic outcomes.
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