Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release
In this report, poly(amide amine) (PAMAM) dendrimer and Heparin-grafted-monomethoxy polyethylene glycol (HEP-mPEG) were synthesized and characterized. In aqueous solution, the generation 4 PAMAM dendrimers (G4.0-PAMAM) existed as nanoparticles with particle size of 5.63nm. However, after electrostat...
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| Veröffentlicht in: | Materials Science & Engineering C 2018-01, Vol.82, p.291-298 |
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| creator | Thanh, Vu Minh Nguyen, Thi Hiep Tran, Tuong Vi Ngoc, Uyen-Thi Phan Ho, Minh Nhat Nguyen, Thi Thinh Chau, Yen Nguyen Tram Le, Van Thu Tran, Ngoc Quyen Nguyen, Cuu Khoa Nguyen, Dai Hai |
| description | In this report, poly(amide amine) (PAMAM) dendrimer and Heparin-grafted-monomethoxy polyethylene glycol (HEP-mPEG) were synthesized and characterized. In aqueous solution, the generation 4 PAMAM dendrimers (G4.0-PAMAM) existed as nanoparticles with particle size of 5.63nm. However, after electrostatic complexation with HEP-mPEG to form a core@shell structure G4.0-PAMAM@HEP-mPEG, the size of nanoparticles was significantly increased (73.82nm). The G4.0-PAMAM@HEP-mPEG nanoparticles showed their ability to effectively encapsulate doxorubicin (DOX) for prolonged and controlled release. The cytocompatibility of G4.0-PAMAM@HEP-mPEG nanocarriers was significantly increased compared with its parentally G4.0-PAMAM dendrimer in both mouse fibroblast NIH3T3 and the human tumor HeLa cell lines. DOX was effectively encapsulated into G4.0-PAMAM@HEP-mPEG nanoparticles to form DOX-loaded nanocarriers (DOX/G4.0-PAMAM@HEP-mPEG) with high loading efficiency (73.2%). The release of DOX from DOX/G4.0-PAMAM@HEP-mPEG nanocarriers was controlled and prolonged up to 96h compared with less than 24h from their parentally G4.0-PAMAM nanocarriers. Importantly, the released DOX retained its bioactivity by inhibiting the proliferation of monolayer-cultured cancer HeLa cells with the same degree of fresh DOX. This prepared G4.0-PAMAM@HEP-mPEG nanocarrier can be a potential candidate for drug delivery systems with high loading capacity and low systemic toxicity in cancer therapy. |
| doi_str_mv | 10.1016/j.msec.2017.07.051 |
| format | Article |
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In aqueous solution, the generation 4 PAMAM dendrimers (G4.0-PAMAM) existed as nanoparticles with particle size of 5.63nm. However, after electrostatic complexation with HEP-mPEG to form a core@shell structure G4.0-PAMAM@HEP-mPEG, the size of nanoparticles was significantly increased (73.82nm). The G4.0-PAMAM@HEP-mPEG nanoparticles showed their ability to effectively encapsulate doxorubicin (DOX) for prolonged and controlled release. The cytocompatibility of G4.0-PAMAM@HEP-mPEG nanocarriers was significantly increased compared with its parentally G4.0-PAMAM dendrimer in both mouse fibroblast NIH3T3 and the human tumor HeLa cell lines. DOX was effectively encapsulated into G4.0-PAMAM@HEP-mPEG nanoparticles to form DOX-loaded nanocarriers (DOX/G4.0-PAMAM@HEP-mPEG) with high loading efficiency (73.2%). The release of DOX from DOX/G4.0-PAMAM@HEP-mPEG nanocarriers was controlled and prolonged up to 96h compared with less than 24h from their parentally G4.0-PAMAM nanocarriers. Importantly, the released DOX retained its bioactivity by inhibiting the proliferation of monolayer-cultured cancer HeLa cells with the same degree of fresh DOX. This prepared G4.0-PAMAM@HEP-mPEG nanocarrier can be a potential candidate for drug delivery systems with high loading capacity and low systemic toxicity in cancer therapy.</description><identifier>ISSN: 0928-4931</identifier><identifier>EISSN: 1873-0191</identifier><identifier>DOI: 10.1016/j.msec.2017.07.051</identifier><identifier>PMID: 29025661</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Bearing strength ; Biocompatibility ; Biological activity ; Cancer ; Cancer therapies ; Cancer therapy ; Cell proliferation ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Controlled release ; Dendrimer ; Dendrimers ; Dendrimers - chemistry ; Doxorubicin ; Doxorubicin - chemistry ; Doxorubicin - metabolism ; Doxorubicin - toxicity ; Drug Carriers - chemical synthesis ; Drug Carriers - chemistry ; Drug Carriers - toxicity ; Drug delivery system ; Drug delivery systems ; Drug Liberation ; Encapsulation ; HeLa Cells ; Heparin ; Heparin - chemistry ; Humans ; Materials science ; Mice ; MPEG encoders ; Nanoparticles ; Nanoparticles - chemistry ; NIH 3T3 Cells ; PAMAM ; Particle Size ; Polyethylene glycol ; Polyethylene Glycols - chemistry ; Spectrophotometry ; Studies ; Toxicity ; Tumor cell lines ; Video compression</subject><ispartof>Materials Science & Engineering C, 2018-01, Vol.82, p.291-298</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV Jan 1, 2018</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-47aec17a3a8d69515398041a01a36857000bd7edd87e0d556cca6def43143ef53</citedby><cites>FETCH-LOGICAL-c384t-47aec17a3a8d69515398041a01a36857000bd7edd87e0d556cca6def43143ef53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.msec.2017.07.051$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29025661$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thanh, Vu Minh</creatorcontrib><creatorcontrib>Nguyen, Thi Hiep</creatorcontrib><creatorcontrib>Tran, Tuong Vi</creatorcontrib><creatorcontrib>Ngoc, Uyen-Thi Phan</creatorcontrib><creatorcontrib>Ho, Minh Nhat</creatorcontrib><creatorcontrib>Nguyen, Thi Thinh</creatorcontrib><creatorcontrib>Chau, Yen Nguyen Tram</creatorcontrib><creatorcontrib>Le, Van Thu</creatorcontrib><creatorcontrib>Tran, Ngoc Quyen</creatorcontrib><creatorcontrib>Nguyen, Cuu Khoa</creatorcontrib><creatorcontrib>Nguyen, Dai Hai</creatorcontrib><title>Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release</title><title>Materials Science & Engineering C</title><addtitle>Mater Sci Eng C Mater Biol Appl</addtitle><description>In this report, poly(amide amine) (PAMAM) dendrimer and Heparin-grafted-monomethoxy polyethylene glycol (HEP-mPEG) were synthesized and characterized. In aqueous solution, the generation 4 PAMAM dendrimers (G4.0-PAMAM) existed as nanoparticles with particle size of 5.63nm. However, after electrostatic complexation with HEP-mPEG to form a core@shell structure G4.0-PAMAM@HEP-mPEG, the size of nanoparticles was significantly increased (73.82nm). The G4.0-PAMAM@HEP-mPEG nanoparticles showed their ability to effectively encapsulate doxorubicin (DOX) for prolonged and controlled release. The cytocompatibility of G4.0-PAMAM@HEP-mPEG nanocarriers was significantly increased compared with its parentally G4.0-PAMAM dendrimer in both mouse fibroblast NIH3T3 and the human tumor HeLa cell lines. DOX was effectively encapsulated into G4.0-PAMAM@HEP-mPEG nanoparticles to form DOX-loaded nanocarriers (DOX/G4.0-PAMAM@HEP-mPEG) with high loading efficiency (73.2%). The release of DOX from DOX/G4.0-PAMAM@HEP-mPEG nanocarriers was controlled and prolonged up to 96h compared with less than 24h from their parentally G4.0-PAMAM nanocarriers. Importantly, the released DOX retained its bioactivity by inhibiting the proliferation of monolayer-cultured cancer HeLa cells with the same degree of fresh DOX. This prepared G4.0-PAMAM@HEP-mPEG nanocarrier can be a potential candidate for drug delivery systems with high loading capacity and low systemic toxicity in cancer therapy.</description><subject>Animals</subject><subject>Bearing strength</subject><subject>Biocompatibility</subject><subject>Biological activity</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cancer therapy</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Controlled release</subject><subject>Dendrimer</subject><subject>Dendrimers</subject><subject>Dendrimers - chemistry</subject><subject>Doxorubicin</subject><subject>Doxorubicin - chemistry</subject><subject>Doxorubicin - metabolism</subject><subject>Doxorubicin - toxicity</subject><subject>Drug Carriers - chemical synthesis</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Carriers - toxicity</subject><subject>Drug delivery system</subject><subject>Drug delivery systems</subject><subject>Drug Liberation</subject><subject>Encapsulation</subject><subject>HeLa Cells</subject><subject>Heparin</subject><subject>Heparin - chemistry</subject><subject>Humans</subject><subject>Materials science</subject><subject>Mice</subject><subject>MPEG encoders</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>NIH 3T3 Cells</subject><subject>PAMAM</subject><subject>Particle Size</subject><subject>Polyethylene glycol</subject><subject>Polyethylene Glycols - chemistry</subject><subject>Spectrophotometry</subject><subject>Studies</subject><subject>Toxicity</subject><subject>Tumor cell lines</subject><subject>Video compression</subject><issn>0928-4931</issn><issn>1873-0191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9vEzEQxS0EoqHwBTggS5w3zKzXf1biElWlRUpFD3C2HHsWHGXXwd4U8u1xmsIR6Ulzee-N3o-xtwhLBFQftsuxkF-2gHoJVRKfsQUaLRrAHp-zBfStabpe4AV7VcoWQBmh25fsou2hlUrhgu3X6RcvxzLTGD2f0-_o43zkk5uSdzlHyoUPbpOjdzMFPuQ08h-0dzlOzXh_fcPdFPj96m51xwNNIcfxMZEy92mac9rtairkw3eeaUeu0Gv2YnC7Qm-e7iX79un669Vts_5y8_lqtW68MN3cdNqRR-2EM0H1EqXoDXToAJ1QRmoA2ARNIRhNEKRU3jsVaOgEdoIGKS7Z-3PvPqefByqz3aZDnupLi70yHaDUfXW1Z5fPqZRMg93XCS4fLYI9QbZbe4JsT5AtVEmsoXdP1YfNSOFf5C_Vavh4NlAd-FAZ2uIjTZ5CzORnG1L8X_8fbU-OXQ</recordid><startdate>20180101</startdate><enddate>20180101</enddate><creator>Thanh, Vu Minh</creator><creator>Nguyen, Thi Hiep</creator><creator>Tran, Tuong Vi</creator><creator>Ngoc, Uyen-Thi Phan</creator><creator>Ho, Minh Nhat</creator><creator>Nguyen, Thi Thinh</creator><creator>Chau, Yen Nguyen Tram</creator><creator>Le, Van Thu</creator><creator>Tran, Ngoc Quyen</creator><creator>Nguyen, Cuu Khoa</creator><creator>Nguyen, Dai Hai</creator><general>Elsevier B.V</general><general>Elsevier BV</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope></search><sort><creationdate>20180101</creationdate><title>Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release</title><author>Thanh, Vu Minh ; Nguyen, Thi Hiep ; Tran, Tuong Vi ; Ngoc, Uyen-Thi Phan ; Ho, Minh Nhat ; Nguyen, Thi Thinh ; Chau, Yen Nguyen Tram ; Le, Van Thu ; Tran, Ngoc Quyen ; Nguyen, Cuu Khoa ; Nguyen, Dai Hai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-47aec17a3a8d69515398041a01a36857000bd7edd87e0d556cca6def43143ef53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Bearing strength</topic><topic>Biocompatibility</topic><topic>Biological activity</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cancer therapy</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Controlled release</topic><topic>Dendrimer</topic><topic>Dendrimers</topic><topic>Dendrimers - chemistry</topic><topic>Doxorubicin</topic><topic>Doxorubicin - chemistry</topic><topic>Doxorubicin - metabolism</topic><topic>Doxorubicin - toxicity</topic><topic>Drug Carriers - chemical synthesis</topic><topic>Drug Carriers - chemistry</topic><topic>Drug Carriers - toxicity</topic><topic>Drug delivery system</topic><topic>Drug delivery systems</topic><topic>Drug Liberation</topic><topic>Encapsulation</topic><topic>HeLa Cells</topic><topic>Heparin</topic><topic>Heparin - chemistry</topic><topic>Humans</topic><topic>Materials science</topic><topic>Mice</topic><topic>MPEG encoders</topic><topic>Nanoparticles</topic><topic>Nanoparticles - chemistry</topic><topic>NIH 3T3 Cells</topic><topic>PAMAM</topic><topic>Particle Size</topic><topic>Polyethylene glycol</topic><topic>Polyethylene Glycols - chemistry</topic><topic>Spectrophotometry</topic><topic>Studies</topic><topic>Toxicity</topic><topic>Tumor cell lines</topic><topic>Video compression</topic><toplevel>online_resources</toplevel><creatorcontrib>Thanh, Vu Minh</creatorcontrib><creatorcontrib>Nguyen, Thi Hiep</creatorcontrib><creatorcontrib>Tran, Tuong Vi</creatorcontrib><creatorcontrib>Ngoc, Uyen-Thi Phan</creatorcontrib><creatorcontrib>Ho, Minh Nhat</creatorcontrib><creatorcontrib>Nguyen, Thi Thinh</creatorcontrib><creatorcontrib>Chau, Yen Nguyen Tram</creatorcontrib><creatorcontrib>Le, Van Thu</creatorcontrib><creatorcontrib>Tran, Ngoc Quyen</creatorcontrib><creatorcontrib>Nguyen, Cuu Khoa</creatorcontrib><creatorcontrib>Nguyen, Dai Hai</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Materials Science & Engineering C</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thanh, Vu Minh</au><au>Nguyen, Thi Hiep</au><au>Tran, Tuong Vi</au><au>Ngoc, Uyen-Thi Phan</au><au>Ho, Minh Nhat</au><au>Nguyen, Thi Thinh</au><au>Chau, Yen Nguyen Tram</au><au>Le, Van Thu</au><au>Tran, Ngoc Quyen</au><au>Nguyen, Cuu Khoa</au><au>Nguyen, Dai Hai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release</atitle><jtitle>Materials Science & Engineering C</jtitle><addtitle>Mater Sci Eng C Mater Biol Appl</addtitle><date>2018-01-01</date><risdate>2018</risdate><volume>82</volume><spage>291</spage><epage>298</epage><pages>291-298</pages><issn>0928-4931</issn><eissn>1873-0191</eissn><abstract>In this report, poly(amide amine) (PAMAM) dendrimer and Heparin-grafted-monomethoxy polyethylene glycol (HEP-mPEG) were synthesized and characterized. In aqueous solution, the generation 4 PAMAM dendrimers (G4.0-PAMAM) existed as nanoparticles with particle size of 5.63nm. However, after electrostatic complexation with HEP-mPEG to form a core@shell structure G4.0-PAMAM@HEP-mPEG, the size of nanoparticles was significantly increased (73.82nm). The G4.0-PAMAM@HEP-mPEG nanoparticles showed their ability to effectively encapsulate doxorubicin (DOX) for prolonged and controlled release. The cytocompatibility of G4.0-PAMAM@HEP-mPEG nanocarriers was significantly increased compared with its parentally G4.0-PAMAM dendrimer in both mouse fibroblast NIH3T3 and the human tumor HeLa cell lines. DOX was effectively encapsulated into G4.0-PAMAM@HEP-mPEG nanoparticles to form DOX-loaded nanocarriers (DOX/G4.0-PAMAM@HEP-mPEG) with high loading efficiency (73.2%). The release of DOX from DOX/G4.0-PAMAM@HEP-mPEG nanocarriers was controlled and prolonged up to 96h compared with less than 24h from their parentally G4.0-PAMAM nanocarriers. Importantly, the released DOX retained its bioactivity by inhibiting the proliferation of monolayer-cultured cancer HeLa cells with the same degree of fresh DOX. This prepared G4.0-PAMAM@HEP-mPEG nanocarrier can be a potential candidate for drug delivery systems with high loading capacity and low systemic toxicity in cancer therapy.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>29025661</pmid><doi>10.1016/j.msec.2017.07.051</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals Bearing strength Biocompatibility Biological activity Cancer Cancer therapies Cancer therapy Cell proliferation Cell Proliferation - drug effects Cell Survival - drug effects Controlled release Dendrimer Dendrimers Dendrimers - chemistry Doxorubicin Doxorubicin - chemistry Doxorubicin - metabolism Doxorubicin - toxicity Drug Carriers - chemical synthesis Drug Carriers - chemistry Drug Carriers - toxicity Drug delivery system Drug delivery systems Drug Liberation Encapsulation HeLa Cells Heparin Heparin - chemistry Humans Materials science Mice MPEG encoders Nanoparticles Nanoparticles - chemistry NIH 3T3 Cells PAMAM Particle Size Polyethylene glycol Polyethylene Glycols - chemistry Spectrophotometry Studies Toxicity Tumor cell lines Video compression |
| title | Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release |
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