Improved anti-tumor activity and safety profile of a paclitaxel-loaded glycyrrhetinic acid-graft-hyaluronic acid conjugate as a synergistically targeted drug delivery system
The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid （HGA） conjugate for intravenous paclitaxel （PTX） delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles （PTX/HGAs） were prepared and characterized by dynamic light scattering measurements. Hem...
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| Veröffentlicht in: | Chinese journal of natural medicines 2015-12, Vol.13 (12), p.915-924 |
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| creator | ZHANG, Li ZHOU, Jian-Ping YAO, Jing |
| description | The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid （HGA） conjugate for intravenous paclitaxel （PTX） delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles （PTX/HGAs） were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer ceils. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio （TIR） being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carder for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects. |
| doi_str_mv | 10.1016/S1875-5364(15)30097-2 |
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Lyophilized PTX-loaded self-assembled HGA nanoparticles （PTX/HGAs） were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer ceils. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio （TIR） being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carder for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects.</description><identifier>ISSN: 2095-6975</identifier><identifier>ISSN: 1875-5364</identifier><identifier>EISSN: 1875-5364</identifier><identifier>DOI: 10.1016/S1875-5364(15)30097-2</identifier><identifier>PMID: 26721710</identifier><language>eng</language><publisher>China: Elsevier B.V</publisher><subject>acid ; activity ; Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - chemistry ; Antitumor ; Antitumor activity ; Apoptosis - drug effects ; Conjugate ; delivery ; Drug Carriers - chemistry ; Drug Delivery Systems - instrumentation ; Drug Delivery Systems - methods ; Drug Synergism ; Female ; Glycyrrhetinic ; Glycyrrhetinic acid ; Glycyrrhetinic Acid - chemistry ; Hep G2 Cells ; Humans ; Hyaluronic ; Hyaluronic acid ; Hyaluronic Acid - chemistry ; Male ; Mice ; Paclitaxel - administration & dosage ; Paclitaxel - adverse effects ; Paclitaxel - chemistry ; Synergistically ; Synergistically targeted delivery ; targeted</subject><ispartof>Chinese journal of natural medicines, 2015-12, Vol.13 (12), p.915-924</ispartof><rights>2015 China Pharmaceutical University</rights><rights>Copyright © 2015 China Pharmaceutical University. 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Lyophilized PTX-loaded self-assembled HGA nanoparticles （PTX/HGAs） were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer ceils. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio （TIR） being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. 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ZHOU, Jian-Ping ; YAO, Jing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-de58cbddd3e5bf572e1408c982678d6a05ad031f6a94671db4bba41c01248acb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>acid</topic><topic>activity</topic><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antitumor</topic><topic>Antitumor activity</topic><topic>Apoptosis - drug effects</topic><topic>Conjugate</topic><topic>delivery</topic><topic>Drug Carriers - chemistry</topic><topic>Drug Delivery Systems - instrumentation</topic><topic>Drug Delivery Systems - methods</topic><topic>Drug Synergism</topic><topic>Female</topic><topic>Glycyrrhetinic</topic><topic>Glycyrrhetinic acid</topic><topic>Glycyrrhetinic Acid - chemistry</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>Hyaluronic</topic><topic>Hyaluronic acid</topic><topic>Hyaluronic Acid - chemistry</topic><topic>Male</topic><topic>Mice</topic><topic>Paclitaxel - administration & dosage</topic><topic>Paclitaxel - adverse effects</topic><topic>Paclitaxel - chemistry</topic><topic>Synergistically</topic><topic>Synergistically targeted delivery</topic><topic>targeted</topic><toplevel>online_resources</toplevel><creatorcontrib>ZHANG, Li</creatorcontrib><creatorcontrib>ZHOU, Jian-Ping</creatorcontrib><creatorcontrib>YAO, Jing</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chinese journal of natural medicines</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ZHANG, Li</au><au>ZHOU, Jian-Ping</au><au>YAO, Jing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improved anti-tumor activity and safety profile of a paclitaxel-loaded glycyrrhetinic acid-graft-hyaluronic acid conjugate as a synergistically targeted drug delivery system</atitle><jtitle>Chinese journal of natural medicines</jtitle><addtitle>Chinese JOurnal of Natural Medicines</addtitle><date>2015-12-01</date><risdate>2015</risdate><volume>13</volume><issue>12</issue><spage>915</spage><epage>924</epage><pages>915-924</pages><issn>2095-6975</issn><issn>1875-5364</issn><eissn>1875-5364</eissn><abstract>The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid （HGA） conjugate for intravenous paclitaxel （PTX） delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles （PTX/HGAs） were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer ceils. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio （TIR） being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. 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| subjects | acid activity Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Antineoplastic Agents - chemistry Antitumor Antitumor activity Apoptosis - drug effects Conjugate delivery Drug Carriers - chemistry Drug Delivery Systems - instrumentation Drug Delivery Systems - methods Drug Synergism Female Glycyrrhetinic Glycyrrhetinic acid Glycyrrhetinic Acid - chemistry Hep G2 Cells Humans Hyaluronic Hyaluronic acid Hyaluronic Acid - chemistry Male Mice Paclitaxel - administration & dosage Paclitaxel - adverse effects Paclitaxel - chemistry Synergistically Synergistically targeted delivery targeted |
| title | Improved anti-tumor activity and safety profile of a paclitaxel-loaded glycyrrhetinic acid-graft-hyaluronic acid conjugate as a synergistically targeted drug delivery system |
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