Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro
Cells of the mononuclear phagocytic system, in particular monocytes/macrophages (Mo/Mac) serve as a reservoir for human immunodeficiency virus (HIV) and are believed to be responsible for its dissemination throughout the body and especially into the brain. Treatment of HIV infection, therefore, must...
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| Veröffentlicht in: | Journal of drug targeting 2007, Vol.15 (1), p.89-98 |
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| creator | Dutta, Tathagata Agashe, Hrushikesh B. Garg, Minakshi Balasubramanium, Prahlad Kabra, Madhulika Jain, Narendra K. |
| description | Cells of the mononuclear phagocytic system, in particular monocytes/macrophages (Mo/Mac) serve as a reservoir for human immunodeficiency virus (HIV) and are believed to be responsible for its dissemination throughout the body and especially into the brain. Treatment of HIV infection, therefore, must reach these cells in addition to the lymphocytes. The purpose of the present study is to develop poly(propyleneimine) (PPI) dendrimer-based nanocontainers for targeting of efavirenz (EFV) to Mo/Mac. Fifth generation PPI dendrimer, t-Boc-glycine conjugated PPI dendrimer (TPPI) and mannose conjugated dendrimers were synthesized and characterized. While the haemolytic activity and cytotoxicity of PPI dendrimer was found to be very high, the toxicity of t-Boc-glycine conjugated dendrimer and mannose conjugated dendrimers were found to be negligible. The entrapment efficiency of mannose conjugated dendrimer was found to be 47.4%, followed by that of PPI dendrimer (32.15%) and t-Boc-glycine conjugated dendrimer (23.1%). The in vitro drug release profile shows that while PPI dendrimer releases the drug by 24 h, the dendrimer-based nanocontainers prolong the release rate up to 144 h (83 ± 0.4% in case of t-Boc-glycine conjugated dendrimer and 91 ± 0.3% in mannose conjugated dendrimer). The cellular uptake of EFV was found to be both concentration and time dependent. Significant increase in cellular uptake of EFV by Mo/Mac cells were observed in case of mannose conjugated dendrimer which is 12 times higher than that of free drug and 5.5 times higher than that of t-Boc-glycine conjugated dendrimer. While mannose conjugated dendrimer was taken up by the lectin receptors of the cells, phagocytosis of t-Boc-glycine conjugated dendrimer might be responsible for its enhanced uptake. Results suggest that the proposed carriers hold potential to increase the efficacy and reduce the toxicity of antiretroviral therapy. |
| doi_str_mv | 10.1080/10611860600965914 |
| format | Article |
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Treatment of HIV infection, therefore, must reach these cells in addition to the lymphocytes. The purpose of the present study is to develop poly(propyleneimine) (PPI) dendrimer-based nanocontainers for targeting of efavirenz (EFV) to Mo/Mac. Fifth generation PPI dendrimer, t-Boc-glycine conjugated PPI dendrimer (TPPI) and mannose conjugated dendrimers were synthesized and characterized. While the haemolytic activity and cytotoxicity of PPI dendrimer was found to be very high, the toxicity of t-Boc-glycine conjugated dendrimer and mannose conjugated dendrimers were found to be negligible. The entrapment efficiency of mannose conjugated dendrimer was found to be 47.4%, followed by that of PPI dendrimer (32.15%) and t-Boc-glycine conjugated dendrimer (23.1%). The in vitro drug release profile shows that while PPI dendrimer releases the drug by 24 h, the dendrimer-based nanocontainers prolong the release rate up to 144 h (83 ± 0.4% in case of t-Boc-glycine conjugated dendrimer and 91 ± 0.3% in mannose conjugated dendrimer). The cellular uptake of EFV was found to be both concentration and time dependent. Significant increase in cellular uptake of EFV by Mo/Mac cells were observed in case of mannose conjugated dendrimer which is 12 times higher than that of free drug and 5.5 times higher than that of t-Boc-glycine conjugated dendrimer. While mannose conjugated dendrimer was taken up by the lectin receptors of the cells, phagocytosis of t-Boc-glycine conjugated dendrimer might be responsible for its enhanced uptake. Results suggest that the proposed carriers hold potential to increase the efficacy and reduce the toxicity of antiretroviral therapy.</description><identifier>ISSN: 1061-186X</identifier><identifier>EISSN: 1029-2330</identifier><identifier>DOI: 10.1080/10611860600965914</identifier><identifier>PMID: 17365278</identifier><language>eng</language><publisher>Abington: Informa UK Ltd</publisher><subject>Benzoxazines - administration & dosage ; Benzoxazines - pharmacology ; Biological and medical sciences ; Cell Line, Tumor ; Cell Survival - drug effects ; Dendrimers ; Drug Compounding ; Drug Delivery Systems ; General pharmacology ; Hemolysis - drug effects ; Human immunodeficiency virus ; Humans ; In Vitro Techniques ; Macrophages - drug effects ; Magnetic Resonance Spectroscopy ; Mannose - chemistry ; Medical sciences ; Monocytes - drug effects ; Nanoparticles ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Polypropylenes - chemistry ; Reverse Transcriptase Inhibitors - administration & dosage ; Reverse Transcriptase Inhibitors - pharmacology ; Spectrophotometry, Infrared</subject><ispartof>Journal of drug targeting, 2007, Vol.15 (1), p.89-98</ispartof><rights>2007 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 2007</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c370t-b459260800b0f4f62b1a557d2d6b3f31d6355a7b344b56bdc9ddbc475050c74a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1080/10611860600965914$$EPDF$$P50$$Ginformahealthcare$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/10611860600965914$$EHTML$$P50$$Ginformahealthcare$$H</linktohtml><link.rule.ids>314,780,784,4022,27922,27923,27924,61220,61255,61401,61436</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18479592$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17365278$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dutta, Tathagata</creatorcontrib><creatorcontrib>Agashe, Hrushikesh B.</creatorcontrib><creatorcontrib>Garg, Minakshi</creatorcontrib><creatorcontrib>Balasubramanium, Prahlad</creatorcontrib><creatorcontrib>Kabra, Madhulika</creatorcontrib><creatorcontrib>Jain, Narendra K.</creatorcontrib><title>Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro</title><title>Journal of drug targeting</title><addtitle>J Drug Target</addtitle><description>Cells of the mononuclear phagocytic system, in particular monocytes/macrophages (Mo/Mac) serve as a reservoir for human immunodeficiency virus (HIV) and are believed to be responsible for its dissemination throughout the body and especially into the brain. Treatment of HIV infection, therefore, must reach these cells in addition to the lymphocytes. The purpose of the present study is to develop poly(propyleneimine) (PPI) dendrimer-based nanocontainers for targeting of efavirenz (EFV) to Mo/Mac. Fifth generation PPI dendrimer, t-Boc-glycine conjugated PPI dendrimer (TPPI) and mannose conjugated dendrimers were synthesized and characterized. While the haemolytic activity and cytotoxicity of PPI dendrimer was found to be very high, the toxicity of t-Boc-glycine conjugated dendrimer and mannose conjugated dendrimers were found to be negligible. The entrapment efficiency of mannose conjugated dendrimer was found to be 47.4%, followed by that of PPI dendrimer (32.15%) and t-Boc-glycine conjugated dendrimer (23.1%). The in vitro drug release profile shows that while PPI dendrimer releases the drug by 24 h, the dendrimer-based nanocontainers prolong the release rate up to 144 h (83 ± 0.4% in case of t-Boc-glycine conjugated dendrimer and 91 ± 0.3% in mannose conjugated dendrimer). The cellular uptake of EFV was found to be both concentration and time dependent. Significant increase in cellular uptake of EFV by Mo/Mac cells were observed in case of mannose conjugated dendrimer which is 12 times higher than that of free drug and 5.5 times higher than that of t-Boc-glycine conjugated dendrimer. While mannose conjugated dendrimer was taken up by the lectin receptors of the cells, phagocytosis of t-Boc-glycine conjugated dendrimer might be responsible for its enhanced uptake. Results suggest that the proposed carriers hold potential to increase the efficacy and reduce the toxicity of antiretroviral therapy.</description><subject>Benzoxazines - administration & dosage</subject><subject>Benzoxazines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Dendrimers</subject><subject>Drug Compounding</subject><subject>Drug Delivery Systems</subject><subject>General pharmacology</subject><subject>Hemolysis - drug effects</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Macrophages - drug effects</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Mannose - chemistry</subject><subject>Medical sciences</subject><subject>Monocytes - drug effects</subject><subject>Nanoparticles</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Polypropylenes - chemistry</subject><subject>Reverse Transcriptase Inhibitors - administration & dosage</subject><subject>Reverse Transcriptase Inhibitors - pharmacology</subject><subject>Spectrophotometry, Infrared</subject><issn>1061-186X</issn><issn>1029-2330</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNplkUtv1TAQhS1ERR_wA9ggb0BlkXYcP5KoK1TxkiqVBUjsovEj97pK7IvtFN3-elz1IhasZqT55mjOGUJeM7hg0MMlA8VYr0ABDEoOTDwjJwzaoWk5h-ePvWJNBX4ek9Oc7wAYVwxekGPWcSXbrj8hv7_FeU_Pdynu9rMLzi8-uPfUumCTX1yiGrOzNGCIJoaCdZoynWKiBdPGFR82NE7UTXjvkwsPtES6XRcMdIl1ZV9cvlzQVPktblymPtB7X1J8SY4mnLN7dahn5Menj9-vvzQ3t5-_Xn-4aQzvoDRayKFV1StomMSkWs1Qys62Vmk-cWYVlxI7zYXQUmlrBmu1EZ0ECaYTyM_Iuyfd6vDX6nIZF5-Nm2cMLq55ZIPsB2hFBd8cwFUvzo67ah_TfvwbVQXeHgDMBucpYTA-_-N60Q312MpdPXE-1JgW3Dqcy9ZgcuNdXFOobkcG4-MDx_8eyP8AcNKNHQ</recordid><startdate>2007</startdate><enddate>2007</enddate><creator>Dutta, Tathagata</creator><creator>Agashe, Hrushikesh B.</creator><creator>Garg, Minakshi</creator><creator>Balasubramanium, Prahlad</creator><creator>Kabra, Madhulika</creator><creator>Jain, Narendra K.</creator><general>Informa UK Ltd</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>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope></search><sort><creationdate>2007</creationdate><title>Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro</title><author>Dutta, Tathagata ; Agashe, Hrushikesh B. ; Garg, Minakshi ; Balasubramanium, Prahlad ; Kabra, Madhulika ; Jain, Narendra K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c370t-b459260800b0f4f62b1a557d2d6b3f31d6355a7b344b56bdc9ddbc475050c74a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Benzoxazines - administration & dosage</topic><topic>Benzoxazines - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Dendrimers</topic><topic>Drug Compounding</topic><topic>Drug Delivery Systems</topic><topic>General pharmacology</topic><topic>Hemolysis - drug effects</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Macrophages - drug effects</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Mannose - chemistry</topic><topic>Medical sciences</topic><topic>Monocytes - drug effects</topic><topic>Nanoparticles</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Polypropylenes - chemistry</topic><topic>Reverse Transcriptase Inhibitors - administration & dosage</topic><topic>Reverse Transcriptase Inhibitors - pharmacology</topic><topic>Spectrophotometry, Infrared</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dutta, Tathagata</creatorcontrib><creatorcontrib>Agashe, Hrushikesh B.</creatorcontrib><creatorcontrib>Garg, Minakshi</creatorcontrib><creatorcontrib>Balasubramanium, Prahlad</creatorcontrib><creatorcontrib>Kabra, Madhulika</creatorcontrib><creatorcontrib>Jain, Narendra K.</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>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of drug targeting</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dutta, Tathagata</au><au>Agashe, Hrushikesh B.</au><au>Garg, Minakshi</au><au>Balasubramanium, Prahlad</au><au>Kabra, Madhulika</au><au>Jain, Narendra K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro</atitle><jtitle>Journal of drug targeting</jtitle><addtitle>J Drug Target</addtitle><date>2007</date><risdate>2007</risdate><volume>15</volume><issue>1</issue><spage>89</spage><epage>98</epage><pages>89-98</pages><issn>1061-186X</issn><eissn>1029-2330</eissn><abstract>Cells of the mononuclear phagocytic system, in particular monocytes/macrophages (Mo/Mac) serve as a reservoir for human immunodeficiency virus (HIV) and are believed to be responsible for its dissemination throughout the body and especially into the brain. Treatment of HIV infection, therefore, must reach these cells in addition to the lymphocytes. The purpose of the present study is to develop poly(propyleneimine) (PPI) dendrimer-based nanocontainers for targeting of efavirenz (EFV) to Mo/Mac. Fifth generation PPI dendrimer, t-Boc-glycine conjugated PPI dendrimer (TPPI) and mannose conjugated dendrimers were synthesized and characterized. While the haemolytic activity and cytotoxicity of PPI dendrimer was found to be very high, the toxicity of t-Boc-glycine conjugated dendrimer and mannose conjugated dendrimers were found to be negligible. The entrapment efficiency of mannose conjugated dendrimer was found to be 47.4%, followed by that of PPI dendrimer (32.15%) and t-Boc-glycine conjugated dendrimer (23.1%). The in vitro drug release profile shows that while PPI dendrimer releases the drug by 24 h, the dendrimer-based nanocontainers prolong the release rate up to 144 h (83 ± 0.4% in case of t-Boc-glycine conjugated dendrimer and 91 ± 0.3% in mannose conjugated dendrimer). The cellular uptake of EFV was found to be both concentration and time dependent. Significant increase in cellular uptake of EFV by Mo/Mac cells were observed in case of mannose conjugated dendrimer which is 12 times higher than that of free drug and 5.5 times higher than that of t-Boc-glycine conjugated dendrimer. While mannose conjugated dendrimer was taken up by the lectin receptors of the cells, phagocytosis of t-Boc-glycine conjugated dendrimer might be responsible for its enhanced uptake. Results suggest that the proposed carriers hold potential to increase the efficacy and reduce the toxicity of antiretroviral therapy.</abstract><cop>Abington</cop><pub>Informa UK Ltd</pub><pmid>17365278</pmid><doi>10.1080/10611860600965914</doi><tpages>10</tpages></addata></record> |
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| subjects | Benzoxazines - administration & dosage Benzoxazines - pharmacology Biological and medical sciences Cell Line, Tumor Cell Survival - drug effects Dendrimers Drug Compounding Drug Delivery Systems General pharmacology Hemolysis - drug effects Human immunodeficiency virus Humans In Vitro Techniques Macrophages - drug effects Magnetic Resonance Spectroscopy Mannose - chemistry Medical sciences Monocytes - drug effects Nanoparticles Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Polypropylenes - chemistry Reverse Transcriptase Inhibitors - administration & dosage Reverse Transcriptase Inhibitors - pharmacology Spectrophotometry, Infrared |
| title | Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro |
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