| Title | Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes |
| Authors | Qin, Jing Yang, Xu Mi, Jia Wang, Jianxin Hou, Jia Shen, Teng Li, Yongji Wang, Bin Li, Xuri Zhu, Weili |
| Affiliation | Fudan Univ, Sch Pharm, Dept Pharmaceut, Key Lab Smart Drug Delivery,Minist Educ, Shanghai 200433, Peoples R China. Heilongjiang Univ Chinese Med, Sch Pharm, Dept Pharmaceut, Harbin, Peoples R China. Fudan Univ, Peoples Hosp 5, Dept Pharm, Shanghai 200433, Peoples R China. Binzhou Med Univ, Yantai, Peoples R China. Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China. Peking Univ, Natl Inst Drug Dependence, 38 Xue Yuan Rd, Beijing 100191, Peoples R China. |
| Keywords | TFF3 drug delivery system monocytes brain-targeting drug delivery antidepressant blood-brain barrier BLOOD-BRAIN-BARRIER MONONUCLEAR-CELLS ENDOTHELIAL-CELLS THP-1 CELLS DEPRESSION MODEL DRUGS MACROPHAGES EXPRESSION MONOCYTES |
| Issue Date | 2014 |
| Publisher | international journal of nanomedicine |
| Citation | INTERNATIONAL JOURNAL OF NANOMEDICINE.2014,9,5247-5257. |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/188512 |
| ISSN | 1178-2013 |
| DOI | 10.2147/OPTH.S69335 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 医学部待认领 |
