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The role of glucose transporters in the distribution of p-aminophenyl-α-d-mannopyranoside modified liposomes within mice brain

The effective treatment of central nervous system diseases is a major challenge due to the presence of the blood–brain barrier (BBB). P-aminophenyl-α-d-mannopyranoside (MAN), a kind of mannose analog, was conjugated onto the surface of liposomes (MAN–LIP) to enhance the brain delivery. In this study...

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Published in:Journal of controlled release 2014-05, Vol.182, p.99-110
Main Authors: Du, Dan, Chang, Naidan, Sun, Shouli, Li, Minghui, Yu, Hui, Liu, Meifang, Liu, Xiaoying, Wang, Guangtian, Li, Haichun, Liu, Xunpei, Geng, Shilong, Wang, Qun, Peng, Haisheng
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creator Du, Dan
Chang, Naidan
Sun, Shouli
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description The effective treatment of central nervous system diseases is a major challenge due to the presence of the blood–brain barrier (BBB). P-aminophenyl-α-d-mannopyranoside (MAN), a kind of mannose analog, was conjugated onto the surface of liposomes (MAN–LIP) to enhance the brain delivery. In this study, we investigated the brain distribution of MAN–LIP based on our previous studies and tried to explore the relationship between the distribution of MAN–LIP and glucose transporters (GLUTs) on the cells. In vivo optical imaging was used to assess the distribution of liposomes in mice brain. The mice administered with MAN–LIP had significantly higher brain fluorescence intensity and MAN–LIP relatively concentrated in the cerebellum and cerebral cortex. Fluorescent microscope and Western blot were used to evaluate the results of lentiviral vector-mediated hSLC2A1 and hSLC2A3 gene transfection into C6, PC12 and vessels of endothelial cell line, bEND.3. The results from live cell station and flow cytometry showed that the cellular uptake of MAN–LIP was significantly improved by GLUT1 and GLUT3 overexpression cells. The transport experiments also demonstrated that the transendothelial ability of MAN–LIP was much stronger when crossing LV-GLUT1/bEND.3 cell monolayers or LV-GLUT3/ bEND.3 cell monolayers, of which GLUT1 and GLUT3 were overexpressed. The combined data indicated that the transcytosis by GLUT1 and GLUT3 was a pathway of MAN–LIP into brain, and the special brain distribution of MAN–LIP was closely related to the non-homogeneous distribution of GLUT1 and GLUT3 in the brain. In this research, a new brain drug delivery system, liposomes modified with p-aminophenyl-α-d-mannopyranoside (MAN–LIP), was prepared. The in vivo optical imaging of mice administered with MAN–LIP showed that there was significantly higher brain fluorescence intensity compared with mice administered with LIP. The ex vivo imaging on excised mouse brains revealed that the brain distribution of MAN–LIP had a notable change along with the time of MAN–LIP treatment. Moreover, a preliminary investigation on the brain targeting mechanism of MAN–LIP was carried out using GLUT overexpression cells. [Display omitted]
doi_str_mv 10.1016/j.jconrel.2014.03.006
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P-aminophenyl-α-d-mannopyranoside (MAN), a kind of mannose analog, was conjugated onto the surface of liposomes (MAN–LIP) to enhance the brain delivery. In this study, we investigated the brain distribution of MAN–LIP based on our previous studies and tried to explore the relationship between the distribution of MAN–LIP and glucose transporters (GLUTs) on the cells. In vivo optical imaging was used to assess the distribution of liposomes in mice brain. The mice administered with MAN–LIP had significantly higher brain fluorescence intensity and MAN–LIP relatively concentrated in the cerebellum and cerebral cortex. Fluorescent microscope and Western blot were used to evaluate the results of lentiviral vector-mediated hSLC2A1 and hSLC2A3 gene transfection into C6, PC12 and vessels of endothelial cell line, bEND.3. The results from live cell station and flow cytometry showed that the cellular uptake of MAN–LIP was significantly improved by GLUT1 and GLUT3 overexpression cells. The transport experiments also demonstrated that the transendothelial ability of MAN–LIP was much stronger when crossing LV-GLUT1/bEND.3 cell monolayers or LV-GLUT3/ bEND.3 cell monolayers, of which GLUT1 and GLUT3 were overexpressed. The combined data indicated that the transcytosis by GLUT1 and GLUT3 was a pathway of MAN–LIP into brain, and the special brain distribution of MAN–LIP was closely related to the non-homogeneous distribution of GLUT1 and GLUT3 in the brain. In this research, a new brain drug delivery system, liposomes modified with p-aminophenyl-α-d-mannopyranoside (MAN–LIP), was prepared. The in vivo optical imaging of mice administered with MAN–LIP showed that there was significantly higher brain fluorescence intensity compared with mice administered with LIP. The ex vivo imaging on excised mouse brains revealed that the brain distribution of MAN–LIP had a notable change along with the time of MAN–LIP treatment. Moreover, a preliminary investigation on the brain targeting mechanism of MAN–LIP was carried out using GLUT overexpression cells. 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P-aminophenyl-α-d-mannopyranoside (MAN), a kind of mannose analog, was conjugated onto the surface of liposomes (MAN–LIP) to enhance the brain delivery. In this study, we investigated the brain distribution of MAN–LIP based on our previous studies and tried to explore the relationship between the distribution of MAN–LIP and glucose transporters (GLUTs) on the cells. In vivo optical imaging was used to assess the distribution of liposomes in mice brain. The mice administered with MAN–LIP had significantly higher brain fluorescence intensity and MAN–LIP relatively concentrated in the cerebellum and cerebral cortex. Fluorescent microscope and Western blot were used to evaluate the results of lentiviral vector-mediated hSLC2A1 and hSLC2A3 gene transfection into C6, PC12 and vessels of endothelial cell line, bEND.3. The results from live cell station and flow cytometry showed that the cellular uptake of MAN–LIP was significantly improved by GLUT1 and GLUT3 overexpression cells. The transport experiments also demonstrated that the transendothelial ability of MAN–LIP was much stronger when crossing LV-GLUT1/bEND.3 cell monolayers or LV-GLUT3/ bEND.3 cell monolayers, of which GLUT1 and GLUT3 were overexpressed. The combined data indicated that the transcytosis by GLUT1 and GLUT3 was a pathway of MAN–LIP into brain, and the special brain distribution of MAN–LIP was closely related to the non-homogeneous distribution of GLUT1 and GLUT3 in the brain. In this research, a new brain drug delivery system, liposomes modified with p-aminophenyl-α-d-mannopyranoside (MAN–LIP), was prepared. The in vivo optical imaging of mice administered with MAN–LIP showed that there was significantly higher brain fluorescence intensity compared with mice administered with LIP. The ex vivo imaging on excised mouse brains revealed that the brain distribution of MAN–LIP had a notable change along with the time of MAN–LIP treatment. Moreover, a preliminary investigation on the brain targeting mechanism of MAN–LIP was carried out using GLUT overexpression cells. [Display omitted]</description><subject>Aniline Compounds - chemistry</subject><subject>Animals</subject><subject>Blood–brain barrier</subject><subject>Brain - metabolism</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Glucose Transporter Type 1 - genetics</subject><subject>Glucose Transporter Type 1 - metabolism</subject><subject>Glucose Transporter Type 3 - genetics</subject><subject>Glucose Transporter Type 3 - metabolism</subject><subject>GLUT1</subject><subject>GLUT3</subject><subject>Liposomes</subject><subject>Liposomes modified with p-aminophenyl-α-d-mannopyranoside</subject><subject>Mannosides - chemistry</subject><subject>Mice</subject><subject>PC12 Cells</subject><subject>Rats</subject><subject>Targeting delivery</subject><subject>Transfection</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNqNkc-KFDEQh4Mo7rj6CEqOXrpNOul0chJZ_LOw4GU9h3RScTJ0J23SrczJZ_JFfCYzzOh1vVRB8f2qoD6EXlLSUkLFm0N7sClmmNqOUN4S1hIiHqEdlQNruFL9Y7SrnGyY6NUVelbKgRDSMz48RVcdF4xKwXbo5_0ecE4T4OTx12mzqQBes4llSXmFXHCIeK2MC2XNYdzWkOKJXRozh5iWPcTj1Pz-1bhmNrEOjjWcSnCA5-SCD-DwFJZU0gwF_wjrvi6cgwU8ZhPic_TEm6nAi0u_Rl8-vL-_-dTcff54e_PurrFMybWRhoP10g4e_OhoD5Rzpwgjo-ip48R1irJRmbHnAzc9CKqYdwpIrU76gV2j1-e9S07fNiirnkOxME0mQtqKpvUzkigh6H-gHWWs6wZZ0f6M2pxKyeD1ksNs8lFTok-a9EFfNOmTJk2Yrppq7tXlxDbO4P6l_nqpwNszAPUn3wNkXWyAaMGFDHbVLoUHTvwBbe6qDQ</recordid><startdate>20140528</startdate><enddate>20140528</enddate><creator>Du, Dan</creator><creator>Chang, Naidan</creator><creator>Sun, Shouli</creator><creator>Li, Minghui</creator><creator>Yu, Hui</creator><creator>Liu, Meifang</creator><creator>Liu, Xiaoying</creator><creator>Wang, Guangtian</creator><creator>Li, Haichun</creator><creator>Liu, Xunpei</creator><creator>Geng, Shilong</creator><creator>Wang, Qun</creator><creator>Peng, Haisheng</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20140528</creationdate><title>The role of glucose transporters in the distribution of p-aminophenyl-α-d-mannopyranoside modified liposomes within mice brain</title><author>Du, Dan ; 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P-aminophenyl-α-d-mannopyranoside (MAN), a kind of mannose analog, was conjugated onto the surface of liposomes (MAN–LIP) to enhance the brain delivery. In this study, we investigated the brain distribution of MAN–LIP based on our previous studies and tried to explore the relationship between the distribution of MAN–LIP and glucose transporters (GLUTs) on the cells. In vivo optical imaging was used to assess the distribution of liposomes in mice brain. The mice administered with MAN–LIP had significantly higher brain fluorescence intensity and MAN–LIP relatively concentrated in the cerebellum and cerebral cortex. Fluorescent microscope and Western blot were used to evaluate the results of lentiviral vector-mediated hSLC2A1 and hSLC2A3 gene transfection into C6, PC12 and vessels of endothelial cell line, bEND.3. The results from live cell station and flow cytometry showed that the cellular uptake of MAN–LIP was significantly improved by GLUT1 and GLUT3 overexpression cells. The transport experiments also demonstrated that the transendothelial ability of MAN–LIP was much stronger when crossing LV-GLUT1/bEND.3 cell monolayers or LV-GLUT3/ bEND.3 cell monolayers, of which GLUT1 and GLUT3 were overexpressed. The combined data indicated that the transcytosis by GLUT1 and GLUT3 was a pathway of MAN–LIP into brain, and the special brain distribution of MAN–LIP was closely related to the non-homogeneous distribution of GLUT1 and GLUT3 in the brain. In this research, a new brain drug delivery system, liposomes modified with p-aminophenyl-α-d-mannopyranoside (MAN–LIP), was prepared. The in vivo optical imaging of mice administered with MAN–LIP showed that there was significantly higher brain fluorescence intensity compared with mice administered with LIP. The ex vivo imaging on excised mouse brains revealed that the brain distribution of MAN–LIP had a notable change along with the time of MAN–LIP treatment. Moreover, a preliminary investigation on the brain targeting mechanism of MAN–LIP was carried out using GLUT overexpression cells. [Display omitted]</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>24631863</pmid><doi>10.1016/j.jconrel.2014.03.006</doi><tpages>12</tpages></addata></record>
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source ScienceDirect Freedom Collection 2022-2024
subjects Aniline Compounds - chemistry
Animals
Blood–brain barrier
Brain - metabolism
Cell Line
Cell Line, Tumor
Glucose Transporter Type 1 - genetics
Glucose Transporter Type 1 - metabolism
Glucose Transporter Type 3 - genetics
Glucose Transporter Type 3 - metabolism
GLUT1
GLUT3
Liposomes
Liposomes modified with p-aminophenyl-α-d-mannopyranoside
Mannosides - chemistry
Mice
PC12 Cells
Rats
Targeting delivery
Transfection
title The role of glucose transporters in the distribution of p-aminophenyl-α-d-mannopyranoside modified liposomes within mice brain
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