title: Monocyte mediated brain targeting delivery of macromolecular drug for the therapy of depression.
abstract: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, China; Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Haerbin, Heilongjiang Province, China; Department of Pharmacy, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing, China.
authors.forename: Ruo-Xi
authors.initials: RX
authors.lastname: Zhang
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing, China.
authors.forename: Yi-Xiao
authors.initials: YX
authors.lastname: Luo
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing, China.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, China; Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Haerbin, Heilongjiang Province, China; Department of Pharmacy, Municipal Hospital, Ministry of Healthcare, Weihai, Shandong Province, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Haerbin, Heilongjiang Province, China.
authors.forename: Yong-Ji
authors.initials: YJ
authors.lastname: Li
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, China. Electronic address: jxwang@fudan.edu.cn.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Wang
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing, China. Electronic address: zhu_wl@bjmu.edu.cn.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003863:Depression / Q000188:drug therapy* / Q000473:pathology; D016503:Drug Delivery Systems; D004357:Drug Synergism; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D051379:Mice; D010455:Peptides / Q000008:administration & dosage*; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D051381:Rats; D000071165:Trefoil Factor-3
chemical_list: D008081:Liposomes; D010455:Peptides; D010456:Peptides, Cyclic; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3; C507169:cyclic arginine-glycine-aspartic acid peptide
keywords: brain-targeting drug delivery system; cRGD; depression; monocyte; trefoil factor 3