University of North Carolina, Chapel Hill, School of Pharmacy, Division of Molecular Pharmaceutics, USA.
Adv Drug Deliv Rev. 2013 Oct;65(10):1331-9. doi: 10.1016/j.addr.2012.07.012. Epub 2012 Aug 17.
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 has 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.
许多药物由于吸收、分布、代谢和排泄等问题而导致治疗活性降低。通过与脂肪酸共形成或共价连接药物，已经显示出一些通过改善肠通透性、减缓清除速度和结合血清蛋白以选择性组织摄取和代谢来克服这些问题的能力。对于口服药物，尽管生物利用度较低，但肠腔中存在脂肪酸和甘油三酯可能会促进小分子亲水性分子的肠内摄取。亲脂性小药物或酰化亲水性药物也显示出增加的淋巴摄取和增强的被动扩散摄取。小分子和大蛋白或肽的脂肪酸缀合已表现出延长的血浆半衰期、在给药时的特定部位递送和持续释放。这些改进很可能是由于与脂质结合的血清蛋白（即白蛋白、LDL 和 HDL）的关联。这些分子相互作用虽然尚未完全阐明，但可能提供利用内源性载体系统改善治疗效果的能力。
