Design, Synthesis, and Biological Evaluation of a Robust, Biodegradable Dendrimer
PEGylated dendrimers are attractive for biological applications due to their tunable pharmacokinetics and ability to carry multiple copies of bioactive molecules. The rapid and efficient synthesis of a robust and biodegradable PEGylated dendrimer based on a polyester−polyamide hybrid core is describ...
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| Veröffentlicht in: | Bioconjugate chemistry 2010-04, Vol.21 (4), p.764-773 |
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| container_title | Bioconjugate chemistry |
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| creator | van der Poll, Derek G Kieler-Ferguson, Heidi M Floyd, William C Guillaudeu, Steven J Jerger, Katherine Szoka, Francis C Fréchet, Jean M |
| description | PEGylated dendrimers are attractive for biological applications due to their tunable pharmacokinetics and ability to carry multiple copies of bioactive molecules. The rapid and efficient synthesis of a robust and biodegradable PEGylated dendrimer based on a polyester−polyamide hybrid core is described. The architecture is designed to avoid destructive side reactions during dendrimer preparation while maintaining biodegradability. Therefore, a dendrimer functionalized with doxorubicin (Dox) was prepared from commercial starting materials in nine, high-yielding linear steps. Both the dendrimer and Doxil were evaluated in parallel using equimolar dosage in the treatment of C26 murine colon carcinoma, leading to statistically equivalent results with most mice tumor-free at the end of the 60 day experiment. The attractive features of this dendritic drug carrier are its simple synthesis, biodegradability, and versatility for application to a variety of drug payloads with high drug loadings. |
| doi_str_mv | 10.1021/bc900553n |
| format | Article |
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The rapid and efficient synthesis of a robust and biodegradable PEGylated dendrimer based on a polyester−polyamide hybrid core is described. The architecture is designed to avoid destructive side reactions during dendrimer preparation while maintaining biodegradability. Therefore, a dendrimer functionalized with doxorubicin (Dox) was prepared from commercial starting materials in nine, high-yielding linear steps. Both the dendrimer and Doxil were evaluated in parallel using equimolar dosage in the treatment of C26 murine colon carcinoma, leading to statistically equivalent results with most mice tumor-free at the end of the 60 day experiment. 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The rapid and efficient synthesis of a robust and biodegradable PEGylated dendrimer based on a polyester−polyamide hybrid core is described. The architecture is designed to avoid destructive side reactions during dendrimer preparation while maintaining biodegradability. Therefore, a dendrimer functionalized with doxorubicin (Dox) was prepared from commercial starting materials in nine, high-yielding linear steps. Both the dendrimer and Doxil were evaluated in parallel using equimolar dosage in the treatment of C26 murine colon carcinoma, leading to statistically equivalent results with most mice tumor-free at the end of the 60 day experiment. The attractive features of this dendritic drug carrier are its simple synthesis, biodegradability, and versatility for application to a variety of drug payloads with high drug loadings.</description><subject>Animals</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colorectal cancer</subject><subject>Dendrimers - chemical synthesis</subject><subject>Dendrimers - metabolism</subject><subject>Dendrimers - pharmacokinetics</subject><subject>Disease Models, Animal</subject><subject>Drug Carriers - chemical synthesis</subject><subject>Drug Carriers - metabolism</subject><subject>Drug Carriers - pharmacokinetics</subject><subject>Drug Design</subject><subject>Female</subject><subject>Medical treatment</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Molecular Structure</subject><subject>Molecules</subject><subject>Nylons - chemistry</subject><subject>Polyesters</subject><subject>Polyesters - chemistry</subject><subject>Polyethylene Glycols - chemical synthesis</subject><subject>Polyethylene Glycols - metabolism</subject><subject>Polyethylene Glycols - pharmacokinetics</subject><subject>Rodents</subject><subject>Tumors</subject><issn>1043-1802</issn><issn>1520-4812</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNplkVtLHTEURkNR6qV98A_IIIgUzrQ7t5nMi-C1CkLpxeeQSfYcR-YkmswI_nsjx55qfcqGLNb-Nh8hOxS-UmD0W2sbACm5_0A2qWRQCkXZWp5B8JIqYBtkK6VbAGioYh_JBgMuOa2aTfLzFFM_97Pi96Mfb_KcZoXxrjjuwxDmvTVDcfZghsmMffBF6ApT_ArtlMbZM-JwHo0z7YDFKXoX-wXGT2S9M0PCzy_vNrk-P_tzclFe_fh-eXJ0VRpR8bFsaycrRFYxRjuKyjqmWqU4Ralszt9xRlXtwFbYdggWa7DAoAMrnOCs5tvkcOm9m9oFOot-jGbQdzmEiY86mF6__fH9jZ6HB82UEk1Fs-DgRRDD_YRp1Is-WRwG4zFMSddSSNHQRmRy7z_yNkzR5-s0Aykgy1iGviwhG0NKEbtVFAr6uSa9qimzu6-zr8i_vWRgfwkYm_4tey96AiAUmLY</recordid><startdate>20100421</startdate><enddate>20100421</enddate><creator>van der Poll, Derek G</creator><creator>Kieler-Ferguson, Heidi M</creator><creator>Floyd, William C</creator><creator>Guillaudeu, Steven J</creator><creator>Jerger, Katherine</creator><creator>Szoka, Francis C</creator><creator>Fréchet, Jean M</creator><general>American Chemical Society</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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20100421</creationdate><title>Design, Synthesis, and Biological Evaluation of a Robust, Biodegradable Dendrimer</title><author>van der Poll, Derek G ; Kieler-Ferguson, Heidi M ; Floyd, William C ; Guillaudeu, Steven J ; Jerger, Katherine ; Szoka, Francis C ; Fréchet, Jean M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a463t-b7d56ee26221f1e8cd28b8831e58c481f32187d0c6ebfe0ce70c020f0c4d43273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Colorectal cancer</topic><topic>Dendrimers - chemical synthesis</topic><topic>Dendrimers - metabolism</topic><topic>Dendrimers - pharmacokinetics</topic><topic>Disease Models, Animal</topic><topic>Drug Carriers - chemical synthesis</topic><topic>Drug Carriers - metabolism</topic><topic>Drug Carriers - pharmacokinetics</topic><topic>Drug Design</topic><topic>Female</topic><topic>Medical treatment</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Molecular Structure</topic><topic>Molecules</topic><topic>Nylons - chemistry</topic><topic>Polyesters</topic><topic>Polyesters - chemistry</topic><topic>Polyethylene Glycols - chemical synthesis</topic><topic>Polyethylene Glycols - metabolism</topic><topic>Polyethylene Glycols - pharmacokinetics</topic><topic>Rodents</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van der Poll, Derek G</creatorcontrib><creatorcontrib>Kieler-Ferguson, Heidi M</creatorcontrib><creatorcontrib>Floyd, William C</creatorcontrib><creatorcontrib>Guillaudeu, Steven J</creatorcontrib><creatorcontrib>Jerger, Katherine</creatorcontrib><creatorcontrib>Szoka, Francis C</creatorcontrib><creatorcontrib>Fréchet, Jean M</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>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bioconjugate chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van der Poll, Derek G</au><au>Kieler-Ferguson, Heidi M</au><au>Floyd, William C</au><au>Guillaudeu, Steven J</au><au>Jerger, Katherine</au><au>Szoka, Francis C</au><au>Fréchet, Jean M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, Synthesis, and Biological Evaluation of a Robust, Biodegradable Dendrimer</atitle><jtitle>Bioconjugate chemistry</jtitle><addtitle>Bioconjugate Chem</addtitle><date>2010-04-21</date><risdate>2010</risdate><volume>21</volume><issue>4</issue><spage>764</spage><epage>773</epage><pages>764-773</pages><issn>1043-1802</issn><eissn>1520-4812</eissn><abstract>PEGylated dendrimers are attractive for biological applications due to their tunable pharmacokinetics and ability to carry multiple copies of bioactive molecules. 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| source | MEDLINE; ACS_美国化学学会期刊（与NSTL共建） |
| subjects | Animals Colonic Neoplasms - drug therapy Colonic Neoplasms - metabolism Colorectal cancer Dendrimers - chemical synthesis Dendrimers - metabolism Dendrimers - pharmacokinetics Disease Models, Animal Drug Carriers - chemical synthesis Drug Carriers - metabolism Drug Carriers - pharmacokinetics Drug Design Female Medical treatment Mice Mice, Inbred BALB C Molecular Structure Molecules Nylons - chemistry Polyesters Polyesters - chemistry Polyethylene Glycols - chemical synthesis Polyethylene Glycols - metabolism Polyethylene Glycols - pharmacokinetics Rodents Tumors |
| title | Design, Synthesis, and Biological Evaluation of a Robust, Biodegradable Dendrimer |
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