Noncovalent Complexation of Amphotericin‑B with Poly(α-glutamic acid)
A noncovalent complex of amphotericin B (AmB) and poly(α-glutamic acid) (PGA) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. The loading of AmB in the complex was in the range of ∼20–50%. AmB was in a highly aggregated state with an aggregation ratio often...
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Veröffentlicht in: | Molecular pharmaceutics 2013-03, Vol.10 (3), p.940-950 |
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creator | Mohamed-Ahmed, Abeer H. A Les, Karolina A Seifert, Karin Croft, Simon L Brocchini, Stephen |
description | A noncovalent complex of amphotericin B (AmB) and poly(α-glutamic acid) (PGA) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. The loading of AmB in the complex was in the range of ∼20–50%. AmB was in a highly aggregated state with an aggregation ratio often above 2.0. This complex (AmB–PGA) was shown to be stable and to have reduced toxicity to human red blood cells and KB cells compared to the parent compound; cell viability was not affected at an AmB concentration as high as 50 and 200 μg/mL respectively. This AmB–PGA complex retained AmB activity against intracellular Leishmania major amastigotes in the differentiated THP-1 cells with an EC50 of 0.07 ± 0.03–0.08 ± 0.01 μg/mL, which is similar to Fungizone (EC50 of 0.06 ± 0.01 μg/mL). The in vitro antileishmanial activity of the complex against Leishmania donovani was retained after storage at 37 °C for 7 days in the form of a solution (EC50 of 0.27 ± 0.03 to 0.35 ± 0.04 μg/mL) and for 30 days as a solid (EC50 of 0.41 ± 0.07 to 0.63 ± 0.25 μg/mL). These encouraging results indicate that the AmB–PGA complex has the potential for further development. |
doi_str_mv | 10.1021/mp300339p |
format | Article |
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A ; Les, Karolina A ; Seifert, Karin ; Croft, Simon L ; Brocchini, Stephen</creator><creatorcontrib>Mohamed-Ahmed, Abeer H. A ; Les, Karolina A ; Seifert, Karin ; Croft, Simon L ; Brocchini, Stephen</creatorcontrib><description>A noncovalent complex of amphotericin B (AmB) and poly(α-glutamic acid) (PGA) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. The loading of AmB in the complex was in the range of ∼20–50%. AmB was in a highly aggregated state with an aggregation ratio often above 2.0. This complex (AmB–PGA) was shown to be stable and to have reduced toxicity to human red blood cells and KB cells compared to the parent compound; cell viability was not affected at an AmB concentration as high as 50 and 200 μg/mL respectively. This AmB–PGA complex retained AmB activity against intracellular Leishmania major amastigotes in the differentiated THP-1 cells with an EC50 of 0.07 ± 0.03–0.08 ± 0.01 μg/mL, which is similar to Fungizone (EC50 of 0.06 ± 0.01 μg/mL). The in vitro antileishmanial activity of the complex against Leishmania donovani was retained after storage at 37 °C for 7 days in the form of a solution (EC50 of 0.27 ± 0.03 to 0.35 ± 0.04 μg/mL) and for 30 days as a solid (EC50 of 0.41 ± 0.07 to 0.63 ± 0.25 μg/mL). These encouraging results indicate that the AmB–PGA complex has the potential for further development.</description><identifier>ISSN: 1543-8384</identifier><identifier>EISSN: 1543-8392</identifier><identifier>DOI: 10.1021/mp300339p</identifier><identifier>PMID: 23234235</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Amphotericin B - chemistry ; Amphotericin B - pharmacology ; Amphotericin B - therapeutic use ; Cell Line ; Glutamic Acid - chemistry ; Humans ; Leishmania donovani - drug effects ; Leishmania major - drug effects ; Leishmania major - pathogenicity ; Leishmaniasis - drug therapy ; Solubility</subject><ispartof>Molecular pharmaceutics, 2013-03, Vol.10 (3), p.940-950</ispartof><rights>Copyright © 2012 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a197t-d1651c5f7e47a267831a398c21507b653cc8efa26ed2db92ff73c598d0aca1d53</citedby><cites>FETCH-LOGICAL-a197t-d1651c5f7e47a267831a398c21507b653cc8efa26ed2db92ff73c598d0aca1d53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/mp300339p$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/mp300339p$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2764,27075,27923,27924,56737,56787</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23234235$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mohamed-Ahmed, Abeer H. A</creatorcontrib><creatorcontrib>Les, Karolina A</creatorcontrib><creatorcontrib>Seifert, Karin</creatorcontrib><creatorcontrib>Croft, Simon L</creatorcontrib><creatorcontrib>Brocchini, Stephen</creatorcontrib><title>Noncovalent Complexation of Amphotericin‑B with Poly(α-glutamic acid)</title><title>Molecular pharmaceutics</title><addtitle>Mol. Pharmaceutics</addtitle><description>A noncovalent complex of amphotericin B (AmB) and poly(α-glutamic acid) (PGA) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. The loading of AmB in the complex was in the range of ∼20–50%. AmB was in a highly aggregated state with an aggregation ratio often above 2.0. This complex (AmB–PGA) was shown to be stable and to have reduced toxicity to human red blood cells and KB cells compared to the parent compound; cell viability was not affected at an AmB concentration as high as 50 and 200 μg/mL respectively. This AmB–PGA complex retained AmB activity against intracellular Leishmania major amastigotes in the differentiated THP-1 cells with an EC50 of 0.07 ± 0.03–0.08 ± 0.01 μg/mL, which is similar to Fungizone (EC50 of 0.06 ± 0.01 μg/mL). The in vitro antileishmanial activity of the complex against Leishmania donovani was retained after storage at 37 °C for 7 days in the form of a solution (EC50 of 0.27 ± 0.03 to 0.35 ± 0.04 μg/mL) and for 30 days as a solid (EC50 of 0.41 ± 0.07 to 0.63 ± 0.25 μg/mL). These encouraging results indicate that the AmB–PGA complex has the potential for further development.</description><subject>Amphotericin B - chemistry</subject><subject>Amphotericin B - pharmacology</subject><subject>Amphotericin B - therapeutic use</subject><subject>Cell Line</subject><subject>Glutamic Acid - chemistry</subject><subject>Humans</subject><subject>Leishmania donovani - drug effects</subject><subject>Leishmania major - drug effects</subject><subject>Leishmania major - pathogenicity</subject><subject>Leishmaniasis - drug therapy</subject><subject>Solubility</subject><issn>1543-8384</issn><issn>1543-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1OwzAUhC0EoqWw4AIoGyS6CNh-cZMsSwQUqQIWsI4c_1BXSWzlp9AdV-AoXIRDcBKCAlmxeiO9T6OZQeiY4HOCKbkoHGAMELsdNCYsAD-CmO4OOgpG6KCu1xjTgFHYRyMKFAIKbIwWd7YUdsNzVTZeYguXq1feGFt6Vnvzwq1soyojTPn19n7pvZhm5T3YfHv2-eE_523DCyM8LoycHqI9zfNaHf3eCXq6vnpMFv7y_uY2mS99TuKw8SWZMSKYDlUQcjoLIyAc4khQwnCYzRgIESndfZSkMoup1iEIFkcSc8GJZDBB095XVLauK6VTV5mCV9uU4PRnjXRYo2NPeta1WaHkQP7V74DTHuCiTte2rcou-j9G3ynRZ-o</recordid><startdate>20130304</startdate><enddate>20130304</enddate><creator>Mohamed-Ahmed, Abeer H. A</creator><creator>Les, Karolina A</creator><creator>Seifert, Karin</creator><creator>Croft, Simon L</creator><creator>Brocchini, Stephen</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></search><sort><creationdate>20130304</creationdate><title>Noncovalent Complexation of Amphotericin‑B with Poly(α-glutamic acid)</title><author>Mohamed-Ahmed, Abeer H. A ; Les, Karolina A ; Seifert, Karin ; Croft, Simon L ; Brocchini, Stephen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a197t-d1651c5f7e47a267831a398c21507b653cc8efa26ed2db92ff73c598d0aca1d53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amphotericin B - chemistry</topic><topic>Amphotericin B - pharmacology</topic><topic>Amphotericin B - therapeutic use</topic><topic>Cell Line</topic><topic>Glutamic Acid - chemistry</topic><topic>Humans</topic><topic>Leishmania donovani - drug effects</topic><topic>Leishmania major - drug effects</topic><topic>Leishmania major - pathogenicity</topic><topic>Leishmaniasis - drug therapy</topic><topic>Solubility</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mohamed-Ahmed, Abeer H. A</creatorcontrib><creatorcontrib>Les, Karolina A</creatorcontrib><creatorcontrib>Seifert, Karin</creatorcontrib><creatorcontrib>Croft, Simon L</creatorcontrib><creatorcontrib>Brocchini, Stephen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Molecular pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mohamed-Ahmed, Abeer H. A</au><au>Les, Karolina A</au><au>Seifert, Karin</au><au>Croft, Simon L</au><au>Brocchini, Stephen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Noncovalent Complexation of Amphotericin‑B with Poly(α-glutamic acid)</atitle><jtitle>Molecular pharmaceutics</jtitle><addtitle>Mol. Pharmaceutics</addtitle><date>2013-03-04</date><risdate>2013</risdate><volume>10</volume><issue>3</issue><spage>940</spage><epage>950</epage><pages>940-950</pages><issn>1543-8384</issn><eissn>1543-8392</eissn><abstract>A noncovalent complex of amphotericin B (AmB) and poly(α-glutamic acid) (PGA) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. The loading of AmB in the complex was in the range of ∼20–50%. AmB was in a highly aggregated state with an aggregation ratio often above 2.0. This complex (AmB–PGA) was shown to be stable and to have reduced toxicity to human red blood cells and KB cells compared to the parent compound; cell viability was not affected at an AmB concentration as high as 50 and 200 μg/mL respectively. This AmB–PGA complex retained AmB activity against intracellular Leishmania major amastigotes in the differentiated THP-1 cells with an EC50 of 0.07 ± 0.03–0.08 ± 0.01 μg/mL, which is similar to Fungizone (EC50 of 0.06 ± 0.01 μg/mL). The in vitro antileishmanial activity of the complex against Leishmania donovani was retained after storage at 37 °C for 7 days in the form of a solution (EC50 of 0.27 ± 0.03 to 0.35 ± 0.04 μg/mL) and for 30 days as a solid (EC50 of 0.41 ± 0.07 to 0.63 ± 0.25 μg/mL). These encouraging results indicate that the AmB–PGA complex has the potential for further development.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>23234235</pmid><doi>10.1021/mp300339p</doi><tpages>11</tpages></addata></record> |
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subjects | Amphotericin B - chemistry Amphotericin B - pharmacology Amphotericin B - therapeutic use Cell Line Glutamic Acid - chemistry Humans Leishmania donovani - drug effects Leishmania major - drug effects Leishmania major - pathogenicity Leishmaniasis - drug therapy Solubility |
title | Noncovalent Complexation of Amphotericin‑B with Poly(α-glutamic acid) |
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