Department of Medicinal Chemistry, Chongqing Institute of Traditional Chinese Medicine , Chongqing , China .
J Drug Target. 2014 Feb;22(2):165-74. doi: 10.3109/1061186X.2013.851683.
Improving efficacy of inflammation treatment by increasing drug delivery to the inflammatory sites is a challenging endeavor. N-formyl-methionyl-leucyl-phenylalanine (fMLP), the first discovered leukocyte chemotaxis peptide, is composed of formyl methionine, leucine and phenylalanine. It conjugates with formyl peptide receptors on the target cells with high receptor expression on the surface such as macrophages. With this in mind, we developed a novel fMLP-modified liposome (fMLP-LIP) for enhancing drug delivery to the inflammatory sites and resolving the systemic reaction issue with conventional anti-inflammatory drugs. Being a more stable and cheaper liposomal component than phospholipids, cholesterol (CHO) has been thoroughly investigated as an alternative anchor. In this study, fMLP was covalently conjugated with CHO with polyethylene glycol link to prepare the liposomes, cellular uptake of liposomes by differentiated human U937 cells was examined and cellular uptake experiment in vitro was employed to optimize fMLP-LIP prescription and investigate the uptake mechanism. An in vivo inflammatory model was established to evaluate the targeting performance of fMLP-LIP to inflammatory site. The in vitro and in vivo findings indicate that the fMLP ligands playing an important role in increasing drug delivery to inflammatory sites and fMLP-LIP as a promising anti-inflammatory drug carrier.
提高药物向炎症部位的递送效率以增强炎症治疗效果是一项极具挑战性的工作。N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）是首个被发现的白细胞趋化肽，由甲硫氨酸、亮氨酸和苯丙氨酸组成。它与目标细胞表面高表达的受体（如巨噬细胞）上的受体结合。有鉴于此，我们开发了一种新型的 fMLP 修饰脂质体（fMLP-LIP），以增强药物向炎症部位的递送，并解决传统抗炎药物的全身反应问题。与磷脂相比，胆固醇（CHO）作为一种更稳定且更廉价的脂质体成分，已被深入研究作为替代锚。在这项研究中，fMLP 通过聚乙二醇键与 CHO 共价连接，制备脂质体，研究了分化的人 U937 细胞对脂质体的摄取，并进行了体外摄取实验，以优化 fMLP-LIP 的处方，并探讨摄取机制。建立了体内炎症模型，以评估 fMLP-LIP 对炎症部位的靶向性能。体外和体内研究结果表明，fMLP 配体在增加药物向炎症部位的递送方面发挥着重要作用，fMLP-LIP 是一种有前途的抗炎药物载体。
