School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
Int J Pharm. 2012 Dec 15;439(1-2):216-22. doi: 10.1016/j.ijpharm.2012.09.038. Epub 2012 Sep 26.
A diverse range of diseases involving the reproductive system are treated with luteinizing hormone-releasing hormone (LHRH) agonists which must be administered daily. Currently, an efficient oral delivery system is not available. Here, we show the facile inclusion of lipoamino acids into the peptide sequence of LHRH, rendering it more stable towards enzymatic degradation, as well as enhancing permeability across Caco-2 cell monolayers. Selected LHRH derivatives were tested in vivo by daily oral administration to rats. The size and weight of the sex organs remained unchanged and the levels of LH were stable over the course of the experiment. However, some of the lipidic peptides (3, 8 and 9) were able to reduce serum levels of follicle-stimulating hormone (FSH), an important finding towards the development of orally available LHRH agonists.
黄体生成素释放激素（LHRH）激动剂可治疗涉及生殖系统的多种疾病，且必须每日给药。目前，尚无有效的口服递送系统。在此，我们将脂氨基酸轻易地整合到 LHRH 的肽序列中，使其对酶降解更稳定，并增强穿过 Caco-2 细胞单层的通透性。通过每日口服给予大鼠，对选定的 LHRH 衍生物进行体内测试。在整个实验过程中，性器官的大小和重量保持不变，LH 水平稳定。然而，一些脂肽（3、8 和 9）能够降低血清中促卵泡激素（FSH）的水平，这是朝着开发可口服的 LHRH 激动剂迈出的重要一步。
