Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes.
Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes.
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通过负载负电荷脂质体增强大分子三叶因子 3 的抗抑郁样作用。
DOI：
10.2147/opth.s69335
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发表时间：
2014
影响因子：
8
通讯作者：
Zhu W
中科院分区：
文献类型：
--
作者：
Qin J;Yang X;Mi J;Wang J;Hou J;Shen T;Li Y;Wang B;Li X;Zhu W
免疫细胞，主要是中性粒细胞和单核细胞，表现出内在的归巢特性，使它们能够迁移到损伤和炎症部位。因此，它们可以充当携带隐藏的药物货物的特洛伊木马，同时穿过不可渗透的屏障，特别是血脑屏障（BBB）迁移到疾病部位。在这项研究中，针对循环吞噬细胞，我们配制了带负电荷的纳米脂质体，并通过pH梯度法将三叶因子3（TFF 3）装载到脂质体中。在优化的处方（脂质：胆固醇为5：1.5，脂质：药物为10：1，脂质浓度为10 mg/mL，磷酸盐缓冲液浓度为10 mmol/L）下，粒径为129.6 nm，Zeta电位为−36.6 mV的TFF 3脂质体的包封率为44.47%。与中性电荷的脂质体相比，带负电荷的脂质体显示出与单核细胞的强结合能力，并且在体外被单核细胞有效地携带穿过血脑屏障。此外，在小鼠的尾部悬吊和强迫游泳试验中发现了增强的抗抑郁样作用，如通过减少不动时间以及增加游泳时间和减少大鼠的不动时间所测量的。这些结果表明，带负电荷的脂质体可以改善TFF 3的行为反应，我们的研究为通过增加BBB的通透性来开发有效的脑疾病治疗开辟了新的途径。
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.
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影响因子：
5.8
作者：
Hwang, SH;Maitani, Y;Nagai, T
通讯作者：
Nagai, T
影响因子：
4.2
作者：
Jonsdottir, Gudrun;Ingolfsdottir, Indiana Elin;Petersen, Petur Henry
通讯作者：
Petersen, Petur Henry
影响因子：
5
作者：
PORSOLT, RD;ANTON, G;JALFRE, M
通讯作者：
JALFRE, M
影响因子：
3.4
作者：
STERU, L;CHERMAT, R;SIMON, P
通讯作者：
SIMON, P
影响因子：
3.3
作者：
Wong, Donald;Prameya, Rukmini;Dorovini-Zis, Katerina
通讯作者：
Dorovini-Zis, Katerina