Loading…
Improvement of oral bioavailability of glycyrrhizin by sodium deoxycholate/phospholipid-mixed nanomicelles
Glycyrrhizin (GL), extracted from the Glycyrrhiza glabra L., is active triterpenoid saponin components. However, due to its impermeability across the gastrointestinal mucosa, oral bioavailability of the drug was relatively low. To improve its oral bioavailability, formulation of GL as sodium deoxych...
Saved in:
Published in: | Journal of drug targeting 2012-08, Vol.20 (7), p.615-622 |
---|---|
Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c448t-d470be6433e18eb86b5f780d5ba63228e5327b244f531423ff543178df1da3ff3 |
---|---|
cites | cdi_FETCH-LOGICAL-c448t-d470be6433e18eb86b5f780d5ba63228e5327b244f531423ff543178df1da3ff3 |
container_end_page | 622 |
container_issue | 7 |
container_start_page | 615 |
container_title | Journal of drug targeting |
container_volume | 20 |
creator | Jin, Shixiao Fu, Shanshan Han, Jin Jin, Shiying Lv, Qingyuan Lu, Yi Qi, Jianping Wu, Wei Yuan, Hailong |
description | Glycyrrhizin (GL), extracted from the Glycyrrhiza glabra L., is active triterpenoid saponin components. However, due to its impermeability across the gastrointestinal mucosa, oral bioavailability of the drug was relatively low. To improve its oral bioavailability, formulation of GL as sodium deoxycholate/phospholipid-mixed nanomicelles (SDC/PL-MMs) has been performed in this study. GL-SDC/PL-MMs were produced by a film dispersion method and then investigated using photon correlation spectroscopy (PCS), zeta potential measurement, as well as its physical stability after storage for 10, 20, 30, 60, 90 and 120 days. To verify the theoretical hypothesis, pharmacokinetics and pharmacodynamic studies based on carbon tetrachloride (CCl4)-induced acute liver injury was investigated. Results showed that a narrow size distributed nanomicelles with a mean particle size of 82.99 ± 7.5 nm and a zeta potential of −32.23 ± 1.05 mV was obtained. In the pharmacokinetics, GL-SDC/PL-MMs show a significant superiority in AUC0-t, Cmax and other pharmacokinetic parameters compared with the control group. In the pharmacodynamic studies, compared with the bifendate control group, GL-SDC/PL-MMs showed an equivalent effect in reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST) and improving the pathological changes of liver tissue. These results revealed that SDC/PL-MMs could enhance GL absorption in gastrointestinal tract and pharmacodynamic effect in the treatment of acute liver injury caused by CCl4, and SDC/PL-MMs might be a good choice for oral delivery of poor bioavailability drug like GL. |
doi_str_mv | 10.3109/1061186X.2012.702770 |
format | article |
fullrecord | <record><control><sourceid>proquest_pasca</sourceid><recordid>TN_cdi_proquest_miscellaneous_1023532034</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1023532034</sourcerecordid><originalsourceid>FETCH-LOGICAL-c448t-d470be6433e18eb86b5f780d5ba63228e5327b244f531423ff543178df1da3ff3</originalsourceid><addsrcrecordid>eNqFkEuLFDEURoMozkP_gUhtBDfVk1dVqjeKDDoODLhRcBduKomVJqm0SdU45a83RXcrbnQR8uDcL_cehF4QvGEEb68Ibgnp2q8bigndCEyFwI_QOcF0W1PG8OP13JJ6Zc7QRc47jAlrCX6KzigVtKV4e452t2Gf4r0JZpyqaKuYwFfKRbgH50E576Zlff_ml35JaXA_3VippcpRuzlU2sSHpR-ih8lc7YeYy_Ju73Qd3IPR1QhjDK433pv8DD2x4LN5ftwv0ZcP7z9ff6zvPt3cXr-7q3vOu6nWXGBlWs6YIZ1RXasaKzqsGwUto7QzDaNCUc5twwinzNqGMyI6bYmGcmOX6PUhtwz2fTZ5ksHltQUYTZyzLIZYycCMF5Qf0D7FnJOxcp9cgLQUSK6W5cmyXC3Lg-VS9vL4w6yC0b-LTloL8OoIQO7B2wRj7_IfrkBYbEnh3h44N9qYAvyIyWs5weJjOhWx_7Ty5q-EwYCfhh6Skbs4p7GI_vcsvwCmBK5-</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1023532034</pqid></control><display><type>article</type><title>Improvement of oral bioavailability of glycyrrhizin by sodium deoxycholate/phospholipid-mixed nanomicelles</title><source>Taylor and Francis:Jisc Collections:Taylor and Francis Read and Publish Agreement 2024-2025:Medical Collection (Reading list)</source><creator>Jin, Shixiao ; Fu, Shanshan ; Han, Jin ; Jin, Shiying ; Lv, Qingyuan ; Lu, Yi ; Qi, Jianping ; Wu, Wei ; Yuan, Hailong</creator><creatorcontrib>Jin, Shixiao ; Fu, Shanshan ; Han, Jin ; Jin, Shiying ; Lv, Qingyuan ; Lu, Yi ; Qi, Jianping ; Wu, Wei ; Yuan, Hailong</creatorcontrib><description>Glycyrrhizin (GL), extracted from the Glycyrrhiza glabra L., is active triterpenoid saponin components. However, due to its impermeability across the gastrointestinal mucosa, oral bioavailability of the drug was relatively low. To improve its oral bioavailability, formulation of GL as sodium deoxycholate/phospholipid-mixed nanomicelles (SDC/PL-MMs) has been performed in this study. GL-SDC/PL-MMs were produced by a film dispersion method and then investigated using photon correlation spectroscopy (PCS), zeta potential measurement, as well as its physical stability after storage for 10, 20, 30, 60, 90 and 120 days. To verify the theoretical hypothesis, pharmacokinetics and pharmacodynamic studies based on carbon tetrachloride (CCl4)-induced acute liver injury was investigated. Results showed that a narrow size distributed nanomicelles with a mean particle size of 82.99 ± 7.5 nm and a zeta potential of −32.23 ± 1.05 mV was obtained. In the pharmacokinetics, GL-SDC/PL-MMs show a significant superiority in AUC0-t, Cmax and other pharmacokinetic parameters compared with the control group. In the pharmacodynamic studies, compared with the bifendate control group, GL-SDC/PL-MMs showed an equivalent effect in reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST) and improving the pathological changes of liver tissue. These results revealed that SDC/PL-MMs could enhance GL absorption in gastrointestinal tract and pharmacodynamic effect in the treatment of acute liver injury caused by CCl4, and SDC/PL-MMs might be a good choice for oral delivery of poor bioavailability drug like GL.</description><identifier>ISSN: 1061-186X</identifier><identifier>EISSN: 1029-2330</identifier><identifier>DOI: 10.3109/1061186X.2012.702770</identifier><identifier>PMID: 22726209</identifier><language>eng</language><publisher>London: Informa Healthcare</publisher><subject>acute liver injury ; Administration, Oral ; Alanine Transaminase - metabolism ; Animals ; Anti-Inflammatory Agents - administration & dosage ; Anti-Inflammatory Agents - pharmacokinetics ; Anti-Inflammatory Agents - therapeutic use ; Aspartate Aminotransferases - metabolism ; Biological and medical sciences ; Biological Availability ; Biphenyl Compounds - therapeutic use ; Carbon Tetrachloride ; Deoxycholic Acid - administration & dosage ; Deoxycholic Acid - chemistry ; Disease Models, Animal ; Drug Stability ; General pharmacology ; Glycyrrhizic Acid - administration & dosage ; Glycyrrhizic Acid - pharmacokinetics ; Glycyrrhizic Acid - therapeutic use ; Glycyrrhizin ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Male ; Medical sciences ; Micelles ; Nanoconjugates - administration & dosage ; Nanoconjugates - chemistry ; oral bioavailability ; Particle Size ; Pharmaceutical technology. Pharmaceutical industry ; pharmacodynamics ; pharmacokinetics ; Pharmacology. Drug treatments ; Phospholipids - administration & dosage ; Phospholipids - chemistry ; Rats ; Rats, Wistar ; sodium deoxycholate/phospholipid-mixed nanomicelles ; Surface Properties</subject><ispartof>Journal of drug targeting, 2012-08, Vol.20 (7), p.615-622</ispartof><rights>2012 Informa UK, Ltd. 2012</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-d470be6433e18eb86b5f780d5ba63228e5327b244f531423ff543178df1da3ff3</citedby><cites>FETCH-LOGICAL-c448t-d470be6433e18eb86b5f780d5ba63228e5327b244f531423ff543178df1da3ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26200791$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22726209$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jin, Shixiao</creatorcontrib><creatorcontrib>Fu, Shanshan</creatorcontrib><creatorcontrib>Han, Jin</creatorcontrib><creatorcontrib>Jin, Shiying</creatorcontrib><creatorcontrib>Lv, Qingyuan</creatorcontrib><creatorcontrib>Lu, Yi</creatorcontrib><creatorcontrib>Qi, Jianping</creatorcontrib><creatorcontrib>Wu, Wei</creatorcontrib><creatorcontrib>Yuan, Hailong</creatorcontrib><title>Improvement of oral bioavailability of glycyrrhizin by sodium deoxycholate/phospholipid-mixed nanomicelles</title><title>Journal of drug targeting</title><addtitle>J Drug Target</addtitle><description>Glycyrrhizin (GL), extracted from the Glycyrrhiza glabra L., is active triterpenoid saponin components. However, due to its impermeability across the gastrointestinal mucosa, oral bioavailability of the drug was relatively low. To improve its oral bioavailability, formulation of GL as sodium deoxycholate/phospholipid-mixed nanomicelles (SDC/PL-MMs) has been performed in this study. GL-SDC/PL-MMs were produced by a film dispersion method and then investigated using photon correlation spectroscopy (PCS), zeta potential measurement, as well as its physical stability after storage for 10, 20, 30, 60, 90 and 120 days. To verify the theoretical hypothesis, pharmacokinetics and pharmacodynamic studies based on carbon tetrachloride (CCl4)-induced acute liver injury was investigated. Results showed that a narrow size distributed nanomicelles with a mean particle size of 82.99 ± 7.5 nm and a zeta potential of −32.23 ± 1.05 mV was obtained. In the pharmacokinetics, GL-SDC/PL-MMs show a significant superiority in AUC0-t, Cmax and other pharmacokinetic parameters compared with the control group. In the pharmacodynamic studies, compared with the bifendate control group, GL-SDC/PL-MMs showed an equivalent effect in reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST) and improving the pathological changes of liver tissue. These results revealed that SDC/PL-MMs could enhance GL absorption in gastrointestinal tract and pharmacodynamic effect in the treatment of acute liver injury caused by CCl4, and SDC/PL-MMs might be a good choice for oral delivery of poor bioavailability drug like GL.</description><subject>acute liver injury</subject><subject>Administration, Oral</subject><subject>Alanine Transaminase - metabolism</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - administration & dosage</subject><subject>Anti-Inflammatory Agents - pharmacokinetics</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Aspartate Aminotransferases - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Biphenyl Compounds - therapeutic use</subject><subject>Carbon Tetrachloride</subject><subject>Deoxycholic Acid - administration & dosage</subject><subject>Deoxycholic Acid - chemistry</subject><subject>Disease Models, Animal</subject><subject>Drug Stability</subject><subject>General pharmacology</subject><subject>Glycyrrhizic Acid - administration & dosage</subject><subject>Glycyrrhizic Acid - pharmacokinetics</subject><subject>Glycyrrhizic Acid - therapeutic use</subject><subject>Glycyrrhizin</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Micelles</subject><subject>Nanoconjugates - administration & dosage</subject><subject>Nanoconjugates - chemistry</subject><subject>oral bioavailability</subject><subject>Particle Size</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>pharmacodynamics</subject><subject>pharmacokinetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Phospholipids - administration & dosage</subject><subject>Phospholipids - chemistry</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>sodium deoxycholate/phospholipid-mixed nanomicelles</subject><subject>Surface Properties</subject><issn>1061-186X</issn><issn>1029-2330</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqFkEuLFDEURoMozkP_gUhtBDfVk1dVqjeKDDoODLhRcBduKomVJqm0SdU45a83RXcrbnQR8uDcL_cehF4QvGEEb68Ibgnp2q8bigndCEyFwI_QOcF0W1PG8OP13JJ6Zc7QRc47jAlrCX6KzigVtKV4e452t2Gf4r0JZpyqaKuYwFfKRbgH50E576Zlff_ml35JaXA_3VippcpRuzlU2sSHpR-ih8lc7YeYy_Ju73Qd3IPR1QhjDK433pv8DD2x4LN5ftwv0ZcP7z9ff6zvPt3cXr-7q3vOu6nWXGBlWs6YIZ1RXasaKzqsGwUto7QzDaNCUc5twwinzNqGMyI6bYmGcmOX6PUhtwz2fTZ5ksHltQUYTZyzLIZYycCMF5Qf0D7FnJOxcp9cgLQUSK6W5cmyXC3Lg-VS9vL4w6yC0b-LTloL8OoIQO7B2wRj7_IfrkBYbEnh3h44N9qYAvyIyWs5weJjOhWx_7Ty5q-EwYCfhh6Skbs4p7GI_vcsvwCmBK5-</recordid><startdate>20120801</startdate><enddate>20120801</enddate><creator>Jin, Shixiao</creator><creator>Fu, Shanshan</creator><creator>Han, Jin</creator><creator>Jin, Shiying</creator><creator>Lv, Qingyuan</creator><creator>Lu, Yi</creator><creator>Qi, Jianping</creator><creator>Wu, Wei</creator><creator>Yuan, Hailong</creator><general>Informa Healthcare</general><general>Taylor & Francis</general><scope>IQODW</scope><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></search><sort><creationdate>20120801</creationdate><title>Improvement of oral bioavailability of glycyrrhizin by sodium deoxycholate/phospholipid-mixed nanomicelles</title><author>Jin, Shixiao ; Fu, Shanshan ; Han, Jin ; Jin, Shiying ; Lv, Qingyuan ; Lu, Yi ; Qi, Jianping ; Wu, Wei ; Yuan, Hailong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-d470be6433e18eb86b5f780d5ba63228e5327b244f531423ff543178df1da3ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>acute liver injury</topic><topic>Administration, Oral</topic><topic>Alanine Transaminase - metabolism</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - administration & dosage</topic><topic>Anti-Inflammatory Agents - pharmacokinetics</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Aspartate Aminotransferases - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>Biphenyl Compounds - therapeutic use</topic><topic>Carbon Tetrachloride</topic><topic>Deoxycholic Acid - administration & dosage</topic><topic>Deoxycholic Acid - chemistry</topic><topic>Disease Models, Animal</topic><topic>Drug Stability</topic><topic>General pharmacology</topic><topic>Glycyrrhizic Acid - administration & dosage</topic><topic>Glycyrrhizic Acid - pharmacokinetics</topic><topic>Glycyrrhizic Acid - therapeutic use</topic><topic>Glycyrrhizin</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Micelles</topic><topic>Nanoconjugates - administration & dosage</topic><topic>Nanoconjugates - chemistry</topic><topic>oral bioavailability</topic><topic>Particle Size</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>pharmacodynamics</topic><topic>pharmacokinetics</topic><topic>Pharmacology. Drug treatments</topic><topic>Phospholipids - administration & dosage</topic><topic>Phospholipids - chemistry</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>sodium deoxycholate/phospholipid-mixed nanomicelles</topic><topic>Surface Properties</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jin, Shixiao</creatorcontrib><creatorcontrib>Fu, Shanshan</creatorcontrib><creatorcontrib>Han, Jin</creatorcontrib><creatorcontrib>Jin, Shiying</creatorcontrib><creatorcontrib>Lv, Qingyuan</creatorcontrib><creatorcontrib>Lu, Yi</creatorcontrib><creatorcontrib>Qi, Jianping</creatorcontrib><creatorcontrib>Wu, Wei</creatorcontrib><creatorcontrib>Yuan, Hailong</creatorcontrib><collection>Pascal-Francis</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>Journal of drug targeting</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jin, Shixiao</au><au>Fu, Shanshan</au><au>Han, Jin</au><au>Jin, Shiying</au><au>Lv, Qingyuan</au><au>Lu, Yi</au><au>Qi, Jianping</au><au>Wu, Wei</au><au>Yuan, Hailong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improvement of oral bioavailability of glycyrrhizin by sodium deoxycholate/phospholipid-mixed nanomicelles</atitle><jtitle>Journal of drug targeting</jtitle><addtitle>J Drug Target</addtitle><date>2012-08-01</date><risdate>2012</risdate><volume>20</volume><issue>7</issue><spage>615</spage><epage>622</epage><pages>615-622</pages><issn>1061-186X</issn><eissn>1029-2330</eissn><abstract>Glycyrrhizin (GL), extracted from the Glycyrrhiza glabra L., is active triterpenoid saponin components. However, due to its impermeability across the gastrointestinal mucosa, oral bioavailability of the drug was relatively low. To improve its oral bioavailability, formulation of GL as sodium deoxycholate/phospholipid-mixed nanomicelles (SDC/PL-MMs) has been performed in this study. GL-SDC/PL-MMs were produced by a film dispersion method and then investigated using photon correlation spectroscopy (PCS), zeta potential measurement, as well as its physical stability after storage for 10, 20, 30, 60, 90 and 120 days. To verify the theoretical hypothesis, pharmacokinetics and pharmacodynamic studies based on carbon tetrachloride (CCl4)-induced acute liver injury was investigated. Results showed that a narrow size distributed nanomicelles with a mean particle size of 82.99 ± 7.5 nm and a zeta potential of −32.23 ± 1.05 mV was obtained. In the pharmacokinetics, GL-SDC/PL-MMs show a significant superiority in AUC0-t, Cmax and other pharmacokinetic parameters compared with the control group. In the pharmacodynamic studies, compared with the bifendate control group, GL-SDC/PL-MMs showed an equivalent effect in reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST) and improving the pathological changes of liver tissue. These results revealed that SDC/PL-MMs could enhance GL absorption in gastrointestinal tract and pharmacodynamic effect in the treatment of acute liver injury caused by CCl4, and SDC/PL-MMs might be a good choice for oral delivery of poor bioavailability drug like GL.</abstract><cop>London</cop><pub>Informa Healthcare</pub><pmid>22726209</pmid><doi>10.3109/1061186X.2012.702770</doi><tpages>8</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1061-186X |
ispartof | Journal of drug targeting, 2012-08, Vol.20 (7), p.615-622 |
issn | 1061-186X 1029-2330 |
language | eng |
recordid | cdi_proquest_miscellaneous_1023532034 |
source | Taylor and Francis:Jisc Collections:Taylor and Francis Read and Publish Agreement 2024-2025:Medical Collection (Reading list) |
subjects | acute liver injury Administration, Oral Alanine Transaminase - metabolism Animals Anti-Inflammatory Agents - administration & dosage Anti-Inflammatory Agents - pharmacokinetics Anti-Inflammatory Agents - therapeutic use Aspartate Aminotransferases - metabolism Biological and medical sciences Biological Availability Biphenyl Compounds - therapeutic use Carbon Tetrachloride Deoxycholic Acid - administration & dosage Deoxycholic Acid - chemistry Disease Models, Animal Drug Stability General pharmacology Glycyrrhizic Acid - administration & dosage Glycyrrhizic Acid - pharmacokinetics Glycyrrhizic Acid - therapeutic use Glycyrrhizin Liver - drug effects Liver - metabolism Liver - pathology Male Medical sciences Micelles Nanoconjugates - administration & dosage Nanoconjugates - chemistry oral bioavailability Particle Size Pharmaceutical technology. Pharmaceutical industry pharmacodynamics pharmacokinetics Pharmacology. Drug treatments Phospholipids - administration & dosage Phospholipids - chemistry Rats Rats, Wistar sodium deoxycholate/phospholipid-mixed nanomicelles Surface Properties |
title | Improvement of oral bioavailability of glycyrrhizin by sodium deoxycholate/phospholipid-mixed nanomicelles |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T19%3A11%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pasca&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Improvement%20of%20oral%20bioavailability%20of%20glycyrrhizin%20by%20sodium%20deoxycholate/phospholipid-mixed%20nanomicelles&rft.jtitle=Journal%20of%20drug%20targeting&rft.au=Jin,%20Shixiao&rft.date=2012-08-01&rft.volume=20&rft.issue=7&rft.spage=615&rft.epage=622&rft.pages=615-622&rft.issn=1061-186X&rft.eissn=1029-2330&rft_id=info:doi/10.3109/1061186X.2012.702770&rft_dat=%3Cproquest_pasca%3E1023532034%3C/proquest_pasca%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c448t-d470be6433e18eb86b5f780d5ba63228e5327b244f531423ff543178df1da3ff3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1023532034&rft_id=info:pmid/22726209&rfr_iscdi=true |