Mechanisms of enhanced antiglioma efficacy of polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles by focused ultrasound
The presence of blood‐brain barrier (BBB) greatly limits the availability of drugs and their efficacy against glioma. Focused ultrasound (FUS) can induce transient and local BBB opening for enhanced drug delivery. Here, we developed polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles (PS‐80...
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| Veröffentlicht in: | Journal of cellular and molecular medicine 2018-09, Vol.22 (9), p.4171-4182 |
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| creator | Li, Yingjia Wu, Manxiang Zhang, Nisi Tang, Caiyun Jiang, Peng Liu, Xin Yan, Fei Zheng, Hairong |
| description | The presence of blood‐brain barrier (BBB) greatly limits the availability of drugs and their efficacy against glioma. Focused ultrasound (FUS) can induce transient and local BBB opening for enhanced drug delivery. Here, we developed polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles (PS‐80‐PTX‐NPs, PPNP) and examined the enhanced local delivery into the brain for glioma treatment by combining with FUS. Our result showed PPNP had good stability, fast drug release rate and significant toxicity to glioma cells. Combined with FUS, PPNP showed a stronger BBB permeation efficiency both in the in vitro and in vivo BBB models. Mechanism studies revealed the disrupted tight junction, reduced P‐glycoprotein expression and ApoE‐dependent PS‐80 permeation collectively contribute to the enhanced drug delivery, resulting in significantly stronger antitumour efficacy and longer survival time in the tumour‐bearing mice. Our study provided a new strategy to efficiently and locally deliver drugs into the brain to treat glioma. |
| doi_str_mv | 10.1111/jcmm.13695 |
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Focused ultrasound (FUS) can induce transient and local BBB opening for enhanced drug delivery. Here, we developed polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles (PS‐80‐PTX‐NPs, PPNP) and examined the enhanced local delivery into the brain for glioma treatment by combining with FUS. Our result showed PPNP had good stability, fast drug release rate and significant toxicity to glioma cells. Combined with FUS, PPNP showed a stronger BBB permeation efficiency both in the in vitro and in vivo BBB models. Mechanism studies revealed the disrupted tight junction, reduced P‐glycoprotein expression and ApoE‐dependent PS‐80 permeation collectively contribute to the enhanced drug delivery, resulting in significantly stronger antitumour efficacy and longer survival time in the tumour‐bearing mice. Our study provided a new strategy to efficiently and locally deliver drugs into the brain to treat glioma.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.13695</identifier><identifier>PMID: 29956460</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Animal models ; Animals ; Antineoplastic Agents, Phytogenic - pharmacokinetics ; Antineoplastic Agents, Phytogenic - pharmacology ; Apolipoprotein E ; Apolipoproteins E - genetics ; Apolipoproteins E - metabolism ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - antagonists & inhibitors ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ; Blood-brain barrier ; Blood-Brain Barrier - drug effects ; Blood-Brain Barrier - metabolism ; Brain ; Brain Neoplasms - metabolism ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; Brain Neoplasms - therapy ; Disease Models, Animal ; Drug Compounding - methods ; Drug delivery ; Drug Delivery Systems - methods ; Drug Liberation ; Extracorporeal Shockwave Therapy - methods ; Female ; focused ultrasound ; Gene Expression ; Glioblastoma - metabolism ; Glioblastoma - mortality ; Glioblastoma - pathology ; Glioblastoma - therapy ; Glioma ; Glioma cells ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nanoparticles ; Nanoparticles - administration & dosage ; Nanoparticles - chemistry ; Nanoparticles - metabolism ; Original ; Paclitaxel ; Paclitaxel - pharmacokinetics ; Paclitaxel - pharmacology ; Polylactide-co-glycolide ; Polyoxyethylene sorbitan monooleate ; polysorbate 80 ; Polysorbates - chemistry ; Survival Analysis ; Tight Junctions - drug effects ; Tight Junctions - metabolism ; Tight Junctions - pathology ; Toxicity ; Tumors ; Ultrasonic imaging ; Ultrasound</subject><ispartof>Journal of cellular and molecular medicine, 2018-09, Vol.22 (9), p.4171-4182</ispartof><rights>2018 Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4485-d045c34bca93a9ea72b035c6564b8bafd1ad16ebcd2b7a28b633e6d32aa5b30b3</citedby><cites>FETCH-LOGICAL-c4485-d045c34bca93a9ea72b035c6564b8bafd1ad16ebcd2b7a28b633e6d32aa5b30b3</cites><orcidid>0000-0003-4874-9582</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111803/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111803/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11561,27923,27924,45573,45574,46051,46475,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29956460$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Yingjia</creatorcontrib><creatorcontrib>Wu, Manxiang</creatorcontrib><creatorcontrib>Zhang, Nisi</creatorcontrib><creatorcontrib>Tang, Caiyun</creatorcontrib><creatorcontrib>Jiang, Peng</creatorcontrib><creatorcontrib>Liu, Xin</creatorcontrib><creatorcontrib>Yan, Fei</creatorcontrib><creatorcontrib>Zheng, Hairong</creatorcontrib><title>Mechanisms of enhanced antiglioma efficacy of polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles by focused ultrasound</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>The presence of blood‐brain barrier (BBB) greatly limits the availability of drugs and their efficacy against glioma. Focused ultrasound (FUS) can induce transient and local BBB opening for enhanced drug delivery. Here, we developed polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles (PS‐80‐PTX‐NPs, PPNP) and examined the enhanced local delivery into the brain for glioma treatment by combining with FUS. Our result showed PPNP had good stability, fast drug release rate and significant toxicity to glioma cells. Combined with FUS, PPNP showed a stronger BBB permeation efficiency both in the in vitro and in vivo BBB models. Mechanism studies revealed the disrupted tight junction, reduced P‐glycoprotein expression and ApoE‐dependent PS‐80 permeation collectively contribute to the enhanced drug delivery, resulting in significantly stronger antitumour efficacy and longer survival time in the tumour‐bearing mice. Our study provided a new strategy to efficiently and locally deliver drugs into the brain to treat glioma.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - pharmacokinetics</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Apolipoprotein E</subject><subject>Apolipoproteins E - genetics</subject><subject>Apolipoproteins E - metabolism</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - antagonists & inhibitors</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Brain</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - mortality</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain Neoplasms - therapy</subject><subject>Disease Models, Animal</subject><subject>Drug Compounding - methods</subject><subject>Drug delivery</subject><subject>Drug Delivery Systems - methods</subject><subject>Drug Liberation</subject><subject>Extracorporeal Shockwave Therapy - methods</subject><subject>Female</subject><subject>focused ultrasound</subject><subject>Gene Expression</subject><subject>Glioblastoma - metabolism</subject><subject>Glioblastoma - mortality</subject><subject>Glioblastoma - pathology</subject><subject>Glioblastoma - therapy</subject><subject>Glioma</subject><subject>Glioma cells</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Nanoparticles</subject><subject>Nanoparticles - administration & dosage</subject><subject>Nanoparticles - chemistry</subject><subject>Nanoparticles - metabolism</subject><subject>Original</subject><subject>Paclitaxel</subject><subject>Paclitaxel - pharmacokinetics</subject><subject>Paclitaxel - pharmacology</subject><subject>Polylactide-co-glycolide</subject><subject>Polyoxyethylene sorbitan monooleate</subject><subject>polysorbate 80</subject><subject>Polysorbates - chemistry</subject><subject>Survival Analysis</subject><subject>Tight Junctions - drug effects</subject><subject>Tight Junctions - metabolism</subject><subject>Tight Junctions - pathology</subject><subject>Toxicity</subject><subject>Tumors</subject><subject>Ultrasonic imaging</subject><subject>Ultrasound</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU9vFCEYxonR2D968QOYSXoz2QrDDIVLk2ajrWY3etAzefkzLRsGpjCjzs2DH6CfsZ9E1l2bepEL8D4_Hl54EHpF8Ckp4-1G9_0poUy0T9AhaXm9aARtnu7XhFN-gI5y3mBMGaHiOTqohWhZw_Ah-rW2-gaCy32uYlfZUDbamgrC6K69iz1UtuucBj1v9SH6OcekYLQVx_c_7_poXOfKgQG0dyP8sL5UfQRTap9XlxdVgBAHSKPT3uZKzVUX9ZSLOvkxQY5TMC_Qsw58ti_38zH6-v7dl-XVYvXp8sPyYrXQTcPbhcFNq2mjNAgKwsJZrTBtNStPUVxBZwgYwqzSplZnUHPFKLXM0BqgVRQreozOd77DpHprtA2lAy-H5HpIs4zg5L9KcDfyOn6TrHwzx7QYnOwNUrydbB7lJk4plJ5ljUVDW86FKNSbHaVTzDnZ7uEGguU2MblNTP5JrMCvH_f0gP6NqABkB3x33s7_sZIfl-v1zvQ35BSncw</recordid><startdate>201809</startdate><enddate>201809</enddate><creator>Li, Yingjia</creator><creator>Wu, Manxiang</creator><creator>Zhang, Nisi</creator><creator>Tang, Caiyun</creator><creator>Jiang, Peng</creator><creator>Liu, Xin</creator><creator>Yan, Fei</creator><creator>Zheng, Hairong</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons 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of enhanced antiglioma efficacy of polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles by focused ultrasound</title><author>Li, Yingjia ; Wu, Manxiang ; Zhang, Nisi ; Tang, Caiyun ; Jiang, Peng ; Liu, Xin ; Yan, Fei ; Zheng, Hairong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4485-d045c34bca93a9ea72b035c6564b8bafd1ad16ebcd2b7a28b633e6d32aa5b30b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Antineoplastic Agents, Phytogenic - pharmacokinetics</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Apolipoprotein E</topic><topic>Apolipoproteins E - genetics</topic><topic>Apolipoproteins E - metabolism</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - antagonists & inhibitors</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Brain</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain Neoplasms - mortality</topic><topic>Brain Neoplasms - pathology</topic><topic>Brain Neoplasms - therapy</topic><topic>Disease Models, Animal</topic><topic>Drug Compounding - methods</topic><topic>Drug delivery</topic><topic>Drug Delivery Systems - methods</topic><topic>Drug Liberation</topic><topic>Extracorporeal Shockwave Therapy - methods</topic><topic>Female</topic><topic>focused ultrasound</topic><topic>Gene Expression</topic><topic>Glioblastoma - metabolism</topic><topic>Glioblastoma - mortality</topic><topic>Glioblastoma - pathology</topic><topic>Glioblastoma - therapy</topic><topic>Glioma</topic><topic>Glioma cells</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Nanoparticles</topic><topic>Nanoparticles - administration & dosage</topic><topic>Nanoparticles - chemistry</topic><topic>Nanoparticles - metabolism</topic><topic>Original</topic><topic>Paclitaxel</topic><topic>Paclitaxel - pharmacokinetics</topic><topic>Paclitaxel - pharmacology</topic><topic>Polylactide-co-glycolide</topic><topic>Polyoxyethylene sorbitan monooleate</topic><topic>polysorbate 80</topic><topic>Polysorbates - chemistry</topic><topic>Survival Analysis</topic><topic>Tight Junctions - drug effects</topic><topic>Tight Junctions - metabolism</topic><topic>Tight Junctions - pathology</topic><topic>Toxicity</topic><topic>Tumors</topic><topic>Ultrasonic imaging</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Yingjia</creatorcontrib><creatorcontrib>Wu, Manxiang</creatorcontrib><creatorcontrib>Zhang, Nisi</creatorcontrib><creatorcontrib>Tang, 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medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Yingjia</au><au>Wu, Manxiang</au><au>Zhang, Nisi</au><au>Tang, Caiyun</au><au>Jiang, Peng</au><au>Liu, Xin</au><au>Yan, Fei</au><au>Zheng, Hairong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanisms of enhanced antiglioma efficacy of polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles by focused ultrasound</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2018-09</date><risdate>2018</risdate><volume>22</volume><issue>9</issue><spage>4171</spage><epage>4182</epage><pages>4171-4182</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>The presence of blood‐brain barrier (BBB) greatly limits the availability of drugs and their efficacy against glioma. Focused ultrasound (FUS) can induce transient and local BBB opening for enhanced drug delivery. Here, we developed polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles (PS‐80‐PTX‐NPs, PPNP) and examined the enhanced local delivery into the brain for glioma treatment by combining with FUS. Our result showed PPNP had good stability, fast drug release rate and significant toxicity to glioma cells. Combined with FUS, PPNP showed a stronger BBB permeation efficiency both in the in vitro and in vivo BBB models. Mechanism studies revealed the disrupted tight junction, reduced P‐glycoprotein expression and ApoE‐dependent PS‐80 permeation collectively contribute to the enhanced drug delivery, resulting in significantly stronger antitumour efficacy and longer survival time in the tumour‐bearing mice. Our study provided a new strategy to efficiently and locally deliver drugs into the brain to treat glioma.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>29956460</pmid><doi>10.1111/jcmm.13695</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-4874-9582</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animal models Animals Antineoplastic Agents, Phytogenic - pharmacokinetics Antineoplastic Agents, Phytogenic - pharmacology Apolipoprotein E Apolipoproteins E - genetics Apolipoproteins E - metabolism ATP Binding Cassette Transporter, Subfamily B, Member 1 - antagonists & inhibitors ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism Blood-brain barrier Blood-Brain Barrier - drug effects Blood-Brain Barrier - metabolism Brain Brain Neoplasms - metabolism Brain Neoplasms - mortality Brain Neoplasms - pathology Brain Neoplasms - therapy Disease Models, Animal Drug Compounding - methods Drug delivery Drug Delivery Systems - methods Drug Liberation Extracorporeal Shockwave Therapy - methods Female focused ultrasound Gene Expression Glioblastoma - metabolism Glioblastoma - mortality Glioblastoma - pathology Glioblastoma - therapy Glioma Glioma cells Humans Mice Mice, Inbred BALB C Mice, Nude Nanoparticles Nanoparticles - administration & dosage Nanoparticles - chemistry Nanoparticles - metabolism Original Paclitaxel Paclitaxel - pharmacokinetics Paclitaxel - pharmacology Polylactide-co-glycolide Polyoxyethylene sorbitan monooleate polysorbate 80 Polysorbates - chemistry Survival Analysis Tight Junctions - drug effects Tight Junctions - metabolism Tight Junctions - pathology Toxicity Tumors Ultrasonic imaging Ultrasound |
| title | Mechanisms of enhanced antiglioma efficacy of polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles by focused ultrasound |
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