title: Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes.
abstract: Immunocytes, mainly neutrophils and monocytes, exhibit an intrinsic homing property, enabling them to migrate to sites of injury and inflammation. They can thus act as Trojan horses carrying concealed drug cargoes while migrating across impermeable barriers to sites of disease, especially the blood-brain barrier (BBB). In this study, to target circulating phagocytic cells, we formulated negatively charged nanosize liposomes and loaded trefoil factor 3 (TFF3) into liposomes by the pH-gradient method. According to the optimized formulation (5:1.5 of lipid to cholesterol, 10:1 of lipid to drug, 10 mg/mL of lipid concentration, and 10 mmol/L of phosphate-buffered saline), 44.47% entrapment efficiency was obtained for TFF3 liposomes with 129.6 nm particle size and -36.6 mV zeta potential. Compared with neutrally charged liposomes, the negatively charged liposomes showed a strong binding capacity with monocytes and were effectively carried by monocytes to cross the BBB in vitro. Furthermore, enhanced antidepressant-like effects were found in the tail-suspension and forced-swim tests in mice, as measured by decreased immobility time, as well as increased swimming time and reduced immobility in rats. These results suggested that negatively charged liposomes could improve the behavioral responses of TFF3, and our study opens up a new way for the development of effective therapies for brain disease by increasing the permeability of the BBB.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, People's Republic of 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, People's Republic of China ; Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China ; Department of Pharmacy, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Binzhou Medical University, Yantai, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Mi
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, People's Republic of China ; Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of 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, People's Republic of China.
authors.forename: Teng
authors.initials: T
authors.lastname: Shen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Yongji
authors.initials: Y
authors.lastname: Li
authors.affiliation: Binzhou Medical University, Yantai, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Binzhou Medical University, Yantai, People's Republic of China.
authors.forename: Xuri
authors.initials: X
authors.lastname: Li
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing, People's Republic of China.
authors.forename: Weili
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000737:chemistry; D001522:Behavior, Animal / Q000187:drug effects*; D004357:Drug Synergism; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071165:Trefoil Factor-3
chemical_list: D000928:Antidepressive Agents; D008081:Liposomes; D010455:Peptides; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3
keywords: TFF3; antidepressant; blood–brain barrier; brain-targeting drug delivery; drug delivery system; monocytes