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

TY - JOUR

T1 - Monocyte mediated brain targeting delivery of macromolecular drug for the therapy of depression

AU - Qin, Jing

AU - Yang, Xu

AU - Zhang, Ruo Xi

AU - Luo, Yi Xiao

AU - Li, Jia Li

AU - Hou, Jia

AU - Zhang, Chun

AU - Li, Yong Ji

AU - Shi, Jie

AU - Lu, Lin

AU - Wang, Jian Xin

AU - Zhu, Wei Li

N1 - Publisher Copyright: © 2015 Elsevier Inc.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

KW - Brain-targeting drug delivery system

KW - CRGD

KW - Depression

KW - Monocyte

KW - Trefoil factor 3

UR - https://www.scopus.com/pages/publications/84922792207

U2 - 10.1016/j.nano.2014.09.012

DO - 10.1016/j.nano.2014.09.012

M3 - Article

C2 - 25461282

SN - 1549-9634

VL - 11

SP - 391

EP - 400

JO - Nanomedicine: Nanotechnology, Biology, and Medicine

JF - Nanomedicine: Nanotechnology, Biology, and Medicine

IS - 2

ER -