The intracellular effects of non-ionic amphiphilic cyclodextrin nanoparticles in the delivery of anticancer drugs
Abstract The aim of this study was to develop nanoparticles made of the amphiphilic cyclodextrin heptakis (2- O -oligo(ethyleneoxide)-6-hexadecylthio-)-β-CD (SC16OH) entrapping docetaxel (Doc) and establish their in vivo potential. Doc-loaded SC16OH nanoparticles were prepared by the emulsion–solven...
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| Veröffentlicht in: | Biomaterials 2009-01, Vol.30 (3), p.374-382 |
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| creator | Quaglia, Fabiana Ostacolo, Luisanna Mazzaglia, Antonino Villari, Valentina Zaccaria, Daniela Sciortino, Maria T |
| description | Abstract The aim of this study was to develop nanoparticles made of the amphiphilic cyclodextrin heptakis (2- O -oligo(ethyleneoxide)-6-hexadecylthio-)-β-CD (SC16OH) entrapping docetaxel (Doc) and establish their in vivo potential. Doc-loaded SC16OH nanoparticles were prepared by the emulsion–solvent evaporation technique and fully characterized for size, zeta potential, amount of entrapped drug, release rate and degradation rate. Spherical vesicular nanoparticles displaying a hydrodynamic radius of about 95 nm which did not change upon storage as an aqueous dispersion, a negative zeta potential and entrapment efficiency of Doc very close to 100% were produced. DSC study highlighted the crystalline nature of SC16OH, unloaded and Doc-loaded SC16OH nanoparticles which resulted in their very slow dissolution during release stage and well-modulated release of entrapped Doc for about 8 weeks. Doc-loaded SC16OH nanoparticles were not hemolytic toward red blood cells as compared to a commercial Doc formulation (Taxotere® ) which shows a dose-dependent toxicity. After exposure of HEp-2 cells to equivalent doses of free Doc and Doc-loaded SC16OH nanoparticles, superior cell killing and cell damage were observed for nanoparticles. Finally, cell damage was attributed to aberrant mitosis which was found to be significantly higher for HEp-2 cells treated with Doc-loaded SC16OH nanoparticles as compared to free Doc likely due to the ability of nanoparticles to slowly release the drug allowing prolonged cell arrest in mitosis. Taken together, these results highlights a great potential of nanoparticles based on SC16OH in solid tumors therapy. |
| doi_str_mv | 10.1016/j.biomaterials.2008.09.035 |
| format | Article |
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Doc-loaded SC16OH nanoparticles were prepared by the emulsion–solvent evaporation technique and fully characterized for size, zeta potential, amount of entrapped drug, release rate and degradation rate. Spherical vesicular nanoparticles displaying a hydrodynamic radius of about 95 nm which did not change upon storage as an aqueous dispersion, a negative zeta potential and entrapment efficiency of Doc very close to 100% were produced. DSC study highlighted the crystalline nature of SC16OH, unloaded and Doc-loaded SC16OH nanoparticles which resulted in their very slow dissolution during release stage and well-modulated release of entrapped Doc for about 8 weeks. Doc-loaded SC16OH nanoparticles were not hemolytic toward red blood cells as compared to a commercial Doc formulation (Taxotere® ) which shows a dose-dependent toxicity. After exposure of HEp-2 cells to equivalent doses of free Doc and Doc-loaded SC16OH nanoparticles, superior cell killing and cell damage were observed for nanoparticles. Finally, cell damage was attributed to aberrant mitosis which was found to be significantly higher for HEp-2 cells treated with Doc-loaded SC16OH nanoparticles as compared to free Doc likely due to the ability of nanoparticles to slowly release the drug allowing prolonged cell arrest in mitosis. Taken together, these results highlights a great potential of nanoparticles based on SC16OH in solid tumors therapy.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2008.09.035</identifier><identifier>PMID: 18930312</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Advanced Basic Science ; Amphiphilic cyclodextrins ; Antineoplastic Agents - pharmacology ; Buffers ; Calorimetry, Differential Scanning ; Cell Line, Tumor ; Cells ; Cyclodextrins - chemistry ; Cyclodextrins - pharmacology ; Dentistry ; Docetaxel ; Drug Carriers - pharmacology ; Drug Delivery Systems ; Electricity ; Erythrocytes - drug effects ; Hemolysis - drug effects ; Humans ; Hydrogen-Ion Concentration - drug effects ; Intracellular Space - drug effects ; Microscopy, Fluorescence ; Nanoparticles ; Nanoparticles - ultrastructure ; Spectrophotometry, Ultraviolet ; Surface-Active Agents - pharmacology ; Taxoids - pharmacology</subject><ispartof>Biomaterials, 2009-01, Vol.30 (3), p.374-382</ispartof><rights>Elsevier Ltd</rights><rights>2008 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-6fa11345f5837326cba872e46c1c0718b665275796cc7c2659be7e80236a7aa93</citedby><cites>FETCH-LOGICAL-c495t-6fa11345f5837326cba872e46c1c0718b665275796cc7c2659be7e80236a7aa93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biomaterials.2008.09.035$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18930312$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Quaglia, Fabiana</creatorcontrib><creatorcontrib>Ostacolo, Luisanna</creatorcontrib><creatorcontrib>Mazzaglia, Antonino</creatorcontrib><creatorcontrib>Villari, Valentina</creatorcontrib><creatorcontrib>Zaccaria, Daniela</creatorcontrib><creatorcontrib>Sciortino, Maria T</creatorcontrib><title>The intracellular effects of non-ionic amphiphilic cyclodextrin nanoparticles in the delivery of anticancer drugs</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract The aim of this study was to develop nanoparticles made of the amphiphilic cyclodextrin heptakis (2- O -oligo(ethyleneoxide)-6-hexadecylthio-)-β-CD (SC16OH) entrapping docetaxel (Doc) and establish their in vivo potential. Doc-loaded SC16OH nanoparticles were prepared by the emulsion–solvent evaporation technique and fully characterized for size, zeta potential, amount of entrapped drug, release rate and degradation rate. Spherical vesicular nanoparticles displaying a hydrodynamic radius of about 95 nm which did not change upon storage as an aqueous dispersion, a negative zeta potential and entrapment efficiency of Doc very close to 100% were produced. DSC study highlighted the crystalline nature of SC16OH, unloaded and Doc-loaded SC16OH nanoparticles which resulted in their very slow dissolution during release stage and well-modulated release of entrapped Doc for about 8 weeks. Doc-loaded SC16OH nanoparticles were not hemolytic toward red blood cells as compared to a commercial Doc formulation (Taxotere® ) which shows a dose-dependent toxicity. After exposure of HEp-2 cells to equivalent doses of free Doc and Doc-loaded SC16OH nanoparticles, superior cell killing and cell damage were observed for nanoparticles. Finally, cell damage was attributed to aberrant mitosis which was found to be significantly higher for HEp-2 cells treated with Doc-loaded SC16OH nanoparticles as compared to free Doc likely due to the ability of nanoparticles to slowly release the drug allowing prolonged cell arrest in mitosis. Taken together, these results highlights a great potential of nanoparticles based on SC16OH in solid tumors therapy.</description><subject>Advanced Basic Science</subject><subject>Amphiphilic cyclodextrins</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Buffers</subject><subject>Calorimetry, Differential Scanning</subject><subject>Cell Line, Tumor</subject><subject>Cells</subject><subject>Cyclodextrins - chemistry</subject><subject>Cyclodextrins - pharmacology</subject><subject>Dentistry</subject><subject>Docetaxel</subject><subject>Drug Carriers - pharmacology</subject><subject>Drug Delivery Systems</subject><subject>Electricity</subject><subject>Erythrocytes - drug effects</subject><subject>Hemolysis - drug effects</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration - drug effects</subject><subject>Intracellular Space - drug effects</subject><subject>Microscopy, Fluorescence</subject><subject>Nanoparticles</subject><subject>Nanoparticles - ultrastructure</subject><subject>Spectrophotometry, Ultraviolet</subject><subject>Surface-Active Agents - pharmacology</subject><subject>Taxoids - pharmacology</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUl2P1CAUJUbjjqN_wTQ--NZ6gQLFBxOzfiab-OD6TCi9dRk7MAvtZuffS51JNL5oQgKEc8-5nHMJeUGhoUDlq13T-7i3MyZvp9wwgK4B3QAXD8iGdqqrhQbxkGyAtqzWkrIL8iTnHZQ7tOwxuaCd5sAp25Db6xusfJiTdThNy2RTheOIbs5VHKsQQ-1j8K6y-8ONL2sqZ3d0Uxzwfk4-VMGGeLBp9m7CXJiquRAOOPk7TMeVw4byZoPDVA1p-Z6fkkdjaRufnfct-fbh_fXlp_rqy8fPl2-vatdqMddytJTyVoyi44oz6XrbKYatdNSBol0vpWBKKC2dU45JoXtU2AHj0iprNd-SlyfeQ4q3C-bZ7H1eP2kDxiUbLqmWnIt_AqkW0PLSxJa8PgFdijknHM0h-b1NR0PBrMmYnfkzGbMmY0Ab-KXy_Kyy9HscfpeeoyiAdycAFlPuPCaTncfi2-BTycMM0f-fzpu_aNzkS4J2-oFHzLu4pLDWUJOZAfN1nZF1RKADUFAs_wmHjbyo</recordid><startdate>20090101</startdate><enddate>20090101</enddate><creator>Quaglia, Fabiana</creator><creator>Ostacolo, Luisanna</creator><creator>Mazzaglia, Antonino</creator><creator>Villari, Valentina</creator><creator>Zaccaria, Daniela</creator><creator>Sciortino, Maria T</creator><general>Elsevier Ltd</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope></search><sort><creationdate>20090101</creationdate><title>The intracellular effects of non-ionic amphiphilic cyclodextrin nanoparticles in the delivery of anticancer drugs</title><author>Quaglia, Fabiana ; Ostacolo, Luisanna ; Mazzaglia, Antonino ; Villari, Valentina ; Zaccaria, Daniela ; Sciortino, Maria T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-6fa11345f5837326cba872e46c1c0718b665275796cc7c2659be7e80236a7aa93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Advanced Basic Science</topic><topic>Amphiphilic cyclodextrins</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Buffers</topic><topic>Calorimetry, Differential Scanning</topic><topic>Cell Line, Tumor</topic><topic>Cells</topic><topic>Cyclodextrins - chemistry</topic><topic>Cyclodextrins - pharmacology</topic><topic>Dentistry</topic><topic>Docetaxel</topic><topic>Drug Carriers - pharmacology</topic><topic>Drug Delivery Systems</topic><topic>Electricity</topic><topic>Erythrocytes - drug effects</topic><topic>Hemolysis - drug effects</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration - drug effects</topic><topic>Intracellular Space - drug effects</topic><topic>Microscopy, Fluorescence</topic><topic>Nanoparticles</topic><topic>Nanoparticles - ultrastructure</topic><topic>Spectrophotometry, Ultraviolet</topic><topic>Surface-Active Agents - pharmacology</topic><topic>Taxoids - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Quaglia, Fabiana</creatorcontrib><creatorcontrib>Ostacolo, Luisanna</creatorcontrib><creatorcontrib>Mazzaglia, Antonino</creatorcontrib><creatorcontrib>Villari, Valentina</creatorcontrib><creatorcontrib>Zaccaria, Daniela</creatorcontrib><creatorcontrib>Sciortino, Maria T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Quaglia, Fabiana</au><au>Ostacolo, Luisanna</au><au>Mazzaglia, Antonino</au><au>Villari, Valentina</au><au>Zaccaria, Daniela</au><au>Sciortino, Maria T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The intracellular effects of non-ionic amphiphilic cyclodextrin nanoparticles in the delivery of anticancer drugs</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2009-01-01</date><risdate>2009</risdate><volume>30</volume><issue>3</issue><spage>374</spage><epage>382</epage><pages>374-382</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract The aim of this study was to develop nanoparticles made of the amphiphilic cyclodextrin heptakis (2- O -oligo(ethyleneoxide)-6-hexadecylthio-)-β-CD (SC16OH) entrapping docetaxel (Doc) and establish their in vivo potential. Doc-loaded SC16OH nanoparticles were prepared by the emulsion–solvent evaporation technique and fully characterized for size, zeta potential, amount of entrapped drug, release rate and degradation rate. Spherical vesicular nanoparticles displaying a hydrodynamic radius of about 95 nm which did not change upon storage as an aqueous dispersion, a negative zeta potential and entrapment efficiency of Doc very close to 100% were produced. DSC study highlighted the crystalline nature of SC16OH, unloaded and Doc-loaded SC16OH nanoparticles which resulted in their very slow dissolution during release stage and well-modulated release of entrapped Doc for about 8 weeks. Doc-loaded SC16OH nanoparticles were not hemolytic toward red blood cells as compared to a commercial Doc formulation (Taxotere® ) which shows a dose-dependent toxicity. After exposure of HEp-2 cells to equivalent doses of free Doc and Doc-loaded SC16OH nanoparticles, superior cell killing and cell damage were observed for nanoparticles. Finally, cell damage was attributed to aberrant mitosis which was found to be significantly higher for HEp-2 cells treated with Doc-loaded SC16OH nanoparticles as compared to free Doc likely due to the ability of nanoparticles to slowly release the drug allowing prolonged cell arrest in mitosis. Taken together, these results highlights a great potential of nanoparticles based on SC16OH in solid tumors therapy.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>18930312</pmid><doi>10.1016/j.biomaterials.2008.09.035</doi><tpages>9</tpages></addata></record> |
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| ispartof | Biomaterials, 2009-01, Vol.30 (3), p.374-382 |
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| subjects | Advanced Basic Science Amphiphilic cyclodextrins Antineoplastic Agents - pharmacology Buffers Calorimetry, Differential Scanning Cell Line, Tumor Cells Cyclodextrins - chemistry Cyclodextrins - pharmacology Dentistry Docetaxel Drug Carriers - pharmacology Drug Delivery Systems Electricity Erythrocytes - drug effects Hemolysis - drug effects Humans Hydrogen-Ion Concentration - drug effects Intracellular Space - drug effects Microscopy, Fluorescence Nanoparticles Nanoparticles - ultrastructure Spectrophotometry, Ultraviolet Surface-Active Agents - pharmacology Taxoids - pharmacology |
| title | The intracellular effects of non-ionic amphiphilic cyclodextrin nanoparticles in the delivery of anticancer drugs |
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