Monocyte mediated brain targeting delivery of macromolecular drug for the therapy of depression

• DOI: 10.1016/j.nano.2014.09.012
• Publication Date: 2014-11-17T03:38:21Z
• Authors: Jing Qin; Xu Yang; Ruo-Xi Zhang; Yi-Xiao Luo; Jia-Li Li; Jia Hou; Chun Zhang; Yong-Ji Li; Jie Shi; Lin Lu; Jian-Xin Wang; Wei-Li Zhu
• Keywords: Male; 0301 basic medicine; Depression; Brain; Drug Synergism; Peptides, Cyclic; Rats; 3. Good health; Mice; 03 medical and health sciences; Drug Delivery Systems; Blood-Brain Barrier; Liposomes; Leukocytes; Animals; Humans; Trefoil Factor-3; Peptides

Leukocytes can cross intact blood-brain barrier under healthy conditions and in many neurological diseases, including psychiatric diseases. In present study, a cyclic RGD (cRGD) peptide with high affinity for integrin receptors of leukocytes was used to modify liposomes. The cRGD-modified liposomes (cRGDL) showed high affinity for monocytes in vitro and in vivo and co-migrated across in vitro BBB model with THP-1. The trefoil factor 3 (TFF3), a macromolecular drug, was rapidly and persistently delivered to brain for at least 12 h when loaded into cRGDL while 2.8-fold increase in drug concentration in basolateral amygdala regions related to depression was observed. A systemic administration of cRGDL-TFF3 mimicked antidepressant-like effect of direct intra-basolateral amygdala administration of TFF3 solution in rats subjected to chronic mild stress. The effective dual-brain targeting delivery resulting from the combination and co-migration of cRGDL with leukocyte cross BBB may be a promising strategy for targeted brain delivery.In an effort to treat depression, brain targeted delivery via monocyte-cRGD liposome complexes capable of crossing the intact BBB was performed in this study in a murine model. Similar approaches may be helpful in the treatment of other neuropsychiatric conditions.