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Design of Biocompatible Chitosan Microgels for Targeted pH-Mediated Intracellular Release of Cancer Therapeutics
We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these mic...
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| Published in: | Biomacromolecules 2006-05, Vol.7 (5), p.1568-1572 |
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| Main Authors: | , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-a409t-77cfead8ed753ec3b9578749b5cf5f9d3b710811bb6b94df992ef9c9bacc53463 |
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| cites | cdi_FETCH-LOGICAL-a409t-77cfead8ed753ec3b9578749b5cf5f9d3b710811bb6b94df992ef9c9bacc53463 |
| container_end_page | 1572 |
| container_issue | 5 |
| container_start_page | 1568 |
| container_title | Biomacromolecules |
| container_volume | 7 |
| creator | Zhang, Hong Mardyani, Sawitri Chan, Warren C. W Kumacheva, Eugenia |
| description | We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects. |
| doi_str_mv | 10.1021/bm050912z |
| format | article |
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W ; Kumacheva, Eugenia</creator><creatorcontrib>Zhang, Hong ; Mardyani, Sawitri ; Chan, Warren C. W ; Kumacheva, Eugenia</creatorcontrib><description>We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects.</description><identifier>ISSN: 1525-7797</identifier><identifier>EISSN: 1526-4602</identifier><identifier>DOI: 10.1021/bm050912z</identifier><identifier>PMID: 16677040</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Antineoplastic Agents - pharmacokinetics ; Antineoplastic Agents - toxicity ; Applied sciences ; Biocompatible Materials - chemical synthesis ; Biological and medical sciences ; Biological Transport ; Cell Survival - drug effects ; Chitosan ; Exact sciences and technology ; Gels ; General pharmacology ; HeLa Cells ; Humans ; Hydrogen-Ion Concentration ; Medical sciences ; Methotrexate - pharmacokinetics ; Methotrexate - toxicity ; Microchemistry ; Molecular Conformation ; Natural polymers ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Physicochemistry of polymers ; Starch and polysaccharides</subject><ispartof>Biomacromolecules, 2006-05, Vol.7 (5), p.1568-1572</ispartof><rights>Copyright © 2006 American Chemical Society</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a409t-77cfead8ed753ec3b9578749b5cf5f9d3b710811bb6b94df992ef9c9bacc53463</citedby><cites>FETCH-LOGICAL-a409t-77cfead8ed753ec3b9578749b5cf5f9d3b710811bb6b94df992ef9c9bacc53463</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=17779634$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16677040$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Hong</creatorcontrib><creatorcontrib>Mardyani, Sawitri</creatorcontrib><creatorcontrib>Chan, Warren C. W</creatorcontrib><creatorcontrib>Kumacheva, Eugenia</creatorcontrib><title>Design of Biocompatible Chitosan Microgels for Targeted pH-Mediated Intracellular Release of Cancer Therapeutics</title><title>Biomacromolecules</title><addtitle>Biomacromolecules</addtitle><description>We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects.</description><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - toxicity</subject><subject>Applied sciences</subject><subject>Biocompatible Materials - chemical synthesis</subject><subject>Biological and medical sciences</subject><subject>Biological Transport</subject><subject>Cell Survival - drug effects</subject><subject>Chitosan</subject><subject>Exact sciences and technology</subject><subject>Gels</subject><subject>General pharmacology</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Medical sciences</subject><subject>Methotrexate - pharmacokinetics</subject><subject>Methotrexate - toxicity</subject><subject>Microchemistry</subject><subject>Molecular Conformation</subject><subject>Natural polymers</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Physicochemistry of polymers</subject><subject>Starch and polysaccharides</subject><issn>1525-7797</issn><issn>1526-4602</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNptkL1PwzAQxS0EoqUw8A-gLAwMATuJ43qE8NFKrZBQmaOzc25d5Ut2MsBfT0orujDdG3737t0j5JrRe0Yj9qAqyqlk0fcJGTMepWGS0uj0V_NQCClG5ML7LaVUxgk_JyOWpkLQhI5J-4zeruugMcGTbXRTtdBZVWKQbWzXeKiDpdWuWWPpA9O4YAVujR0WQTsLl1hY2Ol53TnQWJZ9CS74wBLB484yg1rjsLRBBy32ndX-kpwZKD1eHeaEfL6-rLJZuHh_m2ePixASKrshtTYIxRQLwWPUsZJcTEUiFdeGG1nESjA6ZUypVMmkMFJGaKSWCrTmcZLGE3K39x3Se-_Q5K2zFbivnNF811r-19rA3uzZtlcVFkfyUNMA3B4A8BpK44a_rD9yYig5jZMjB9rn26Z39fDiPwd_AKYUgoM</recordid><startdate>20060501</startdate><enddate>20060501</enddate><creator>Zhang, Hong</creator><creator>Mardyani, Sawitri</creator><creator>Chan, Warren C. 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W ; Kumacheva, Eugenia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a409t-77cfead8ed753ec3b9578749b5cf5f9d3b710811bb6b94df992ef9c9bacc53463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - toxicity</topic><topic>Applied sciences</topic><topic>Biocompatible Materials - chemical synthesis</topic><topic>Biological and medical sciences</topic><topic>Biological Transport</topic><topic>Cell Survival - drug effects</topic><topic>Chitosan</topic><topic>Exact sciences and technology</topic><topic>Gels</topic><topic>General pharmacology</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Medical sciences</topic><topic>Methotrexate - pharmacokinetics</topic><topic>Methotrexate - toxicity</topic><topic>Microchemistry</topic><topic>Molecular Conformation</topic><topic>Natural polymers</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Physicochemistry of polymers</topic><topic>Starch and polysaccharides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Hong</creatorcontrib><creatorcontrib>Mardyani, Sawitri</creatorcontrib><creatorcontrib>Chan, Warren C. W</creatorcontrib><creatorcontrib>Kumacheva, Eugenia</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><jtitle>Biomacromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Hong</au><au>Mardyani, Sawitri</au><au>Chan, Warren C. 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When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>16677040</pmid><doi>10.1021/bm050912z</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1525-7797 |
| ispartof | Biomacromolecules, 2006-05, Vol.7 (5), p.1568-1572 |
| issn | 1525-7797 1526-4602 |
| language | eng |
| recordid | cdi_crossref_primary_10_1021_bm050912z |
| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| subjects | Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - toxicity Applied sciences Biocompatible Materials - chemical synthesis Biological and medical sciences Biological Transport Cell Survival - drug effects Chitosan Exact sciences and technology Gels General pharmacology HeLa Cells Humans Hydrogen-Ion Concentration Medical sciences Methotrexate - pharmacokinetics Methotrexate - toxicity Microchemistry Molecular Conformation Natural polymers Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Physicochemistry of polymers Starch and polysaccharides |
| title | Design of Biocompatible Chitosan Microgels for Targeted pH-Mediated Intracellular Release of Cancer Therapeutics |
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