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Evaluation of Safety and Antileishmanial Efficacy of Amine Functionalized Carbon-Based Composite Nanoparticle Appended With Amphotericin B: An in vitro and Preclinical Study
Visceral leishmaniasis (VL) has been a major health concern in the developing world, primarily affecting impoverished people. It is caused by a protozoan parasite and is characterized by immune dysfunction that can lead to deadly secondary infections. Several adverse side effects limit the existing...
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Published in: | Frontiers in chemistry 2020-07, Vol.8, p.510 |
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creator | Gedda, Mallikarjuna Rao Madhukar, Prasoon Vishwakarma, Alok Kumar Verma, Vimal Kushwaha, Anurag Kumar Yadagiri, Ganesh Mudavath, Shyam Lal Singh, Om Prakash Srivastava, Onkar Nath Sundar, Shyam |
description | Visceral leishmaniasis (VL) has been a major health concern in the developing world, primarily affecting impoverished people. It is caused by a protozoan parasite
and is characterized by immune dysfunction that can lead to deadly secondary infections. Several adverse side effects limit the existing treatment options; hence, the need of the hour is some drug option with high efficacy and no toxicity. To make targeted delivery of Amphotericin B (AmB), we have used amine-functionalized versions of carbon nanostructures, namely f-CNT and f-Graphene (f-Grap). The results with f-Grap-AmB, because of a much larger surface area, were expected to be better. However, the results obtained by us showed only marginal improvement (IC50 f-Grap-AmB; 0.0038 ± 0.00119 μg/mL). This is, in all likelihood, due to the agglomeration effect of f-Grap-AmB, which is invariably obtained with graphene. To resolve this issue, we have synthesized a graphene-CNT composite (graphene 70% and CNT 30% by weight). Because CNT is dispersed in between graphene sheets, the agglomeration effect is avoided, and our study suggests that the f-Composite-AmB (f-Comp-AmB) showed no toxicity against the murine J774A.1 macrophage cell line and did not induce any hepatic or renal toxicity in Swiss albino mice. The f-Comp-AmB also showed a remarkable elevation in the
and
antileishmanial efficacy in comparison to AmB and f-CNT-AmB or f-Grap-AmB in J774A.1 and Golden Syrian hamsters, respectively. Additionally, we have also observed that the percentage suppression of parasite replication in the spleen of the hamster was significantly higher in the f-Comp-AmB (97.79 ± 0.2375) treated group in comparison with the AmB (85.66 ± 1.164) treated group of hamsters. To conclude, f-Comp-AmB could be a safe and reliable therapeutic option over the other carbon-based nanoparticles (NPs), i.e., f-CNT-AmB, f-Grap-AmB, and conventional AmB. |
doi_str_mv | 10.3389/fchem.2020.00510 |
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and is characterized by immune dysfunction that can lead to deadly secondary infections. Several adverse side effects limit the existing treatment options; hence, the need of the hour is some drug option with high efficacy and no toxicity. To make targeted delivery of Amphotericin B (AmB), we have used amine-functionalized versions of carbon nanostructures, namely f-CNT and f-Graphene (f-Grap). The results with f-Grap-AmB, because of a much larger surface area, were expected to be better. However, the results obtained by us showed only marginal improvement (IC50 f-Grap-AmB; 0.0038 ± 0.00119 μg/mL). This is, in all likelihood, due to the agglomeration effect of f-Grap-AmB, which is invariably obtained with graphene. To resolve this issue, we have synthesized a graphene-CNT composite (graphene 70% and CNT 30% by weight). Because CNT is dispersed in between graphene sheets, the agglomeration effect is avoided, and our study suggests that the f-Composite-AmB (f-Comp-AmB) showed no toxicity against the murine J774A.1 macrophage cell line and did not induce any hepatic or renal toxicity in Swiss albino mice. The f-Comp-AmB also showed a remarkable elevation in the
and
antileishmanial efficacy in comparison to AmB and f-CNT-AmB or f-Grap-AmB in J774A.1 and Golden Syrian hamsters, respectively. Additionally, we have also observed that the percentage suppression of parasite replication in the spleen of the hamster was significantly higher in the f-Comp-AmB (97.79 ± 0.2375) treated group in comparison with the AmB (85.66 ± 1.164) treated group of hamsters. To conclude, f-Comp-AmB could be a safe and reliable therapeutic option over the other carbon-based nanoparticles (NPs), i.e., f-CNT-AmB, f-Grap-AmB, and conventional AmB.</description><identifier>ISSN: 2296-2646</identifier><identifier>EISSN: 2296-2646</identifier><identifier>DOI: 10.3389/fchem.2020.00510</identifier><identifier>PMID: 32719770</identifier><language>eng</language><publisher>Switzerland: Frontiers Media S.A</publisher><subject>antileishmanial activity ; Chemistry ; cytotoxicity ; graphene-CNT composite ; nanoparticles ; visceral leishmaniasis</subject><ispartof>Frontiers in chemistry, 2020-07, Vol.8, p.510</ispartof><rights>Copyright © 2020 Gedda, Madhukar, Vishwakarma, Verma, Kushwaha, Yadagiri, Mudavath, Singh, Srivastava and Sundar.</rights><rights>Copyright © 2020 Gedda, Madhukar, Vishwakarma, Verma, Kushwaha, Yadagiri, Mudavath, Singh, Srivastava and Sundar. 2020 Gedda, Madhukar, Vishwakarma, Verma, Kushwaha, Yadagiri, Mudavath, Singh, Srivastava and Sundar</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3770-a35b4b93259148ff8a345ada54f3c5ce7915f2316cf88ea158810f32cfee85f3</citedby><cites>FETCH-LOGICAL-c3770-a35b4b93259148ff8a345ada54f3c5ce7915f2316cf88ea158810f32cfee85f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350933/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350933/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32719770$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gedda, Mallikarjuna Rao</creatorcontrib><creatorcontrib>Madhukar, Prasoon</creatorcontrib><creatorcontrib>Vishwakarma, Alok Kumar</creatorcontrib><creatorcontrib>Verma, Vimal</creatorcontrib><creatorcontrib>Kushwaha, Anurag Kumar</creatorcontrib><creatorcontrib>Yadagiri, Ganesh</creatorcontrib><creatorcontrib>Mudavath, Shyam Lal</creatorcontrib><creatorcontrib>Singh, Om Prakash</creatorcontrib><creatorcontrib>Srivastava, Onkar Nath</creatorcontrib><creatorcontrib>Sundar, Shyam</creatorcontrib><title>Evaluation of Safety and Antileishmanial Efficacy of Amine Functionalized Carbon-Based Composite Nanoparticle Appended With Amphotericin B: An in vitro and Preclinical Study</title><title>Frontiers in chemistry</title><addtitle>Front Chem</addtitle><description>Visceral leishmaniasis (VL) has been a major health concern in the developing world, primarily affecting impoverished people. It is caused by a protozoan parasite
and is characterized by immune dysfunction that can lead to deadly secondary infections. Several adverse side effects limit the existing treatment options; hence, the need of the hour is some drug option with high efficacy and no toxicity. To make targeted delivery of Amphotericin B (AmB), we have used amine-functionalized versions of carbon nanostructures, namely f-CNT and f-Graphene (f-Grap). The results with f-Grap-AmB, because of a much larger surface area, were expected to be better. However, the results obtained by us showed only marginal improvement (IC50 f-Grap-AmB; 0.0038 ± 0.00119 μg/mL). This is, in all likelihood, due to the agglomeration effect of f-Grap-AmB, which is invariably obtained with graphene. To resolve this issue, we have synthesized a graphene-CNT composite (graphene 70% and CNT 30% by weight). Because CNT is dispersed in between graphene sheets, the agglomeration effect is avoided, and our study suggests that the f-Composite-AmB (f-Comp-AmB) showed no toxicity against the murine J774A.1 macrophage cell line and did not induce any hepatic or renal toxicity in Swiss albino mice. The f-Comp-AmB also showed a remarkable elevation in the
and
antileishmanial efficacy in comparison to AmB and f-CNT-AmB or f-Grap-AmB in J774A.1 and Golden Syrian hamsters, respectively. Additionally, we have also observed that the percentage suppression of parasite replication in the spleen of the hamster was significantly higher in the f-Comp-AmB (97.79 ± 0.2375) treated group in comparison with the AmB (85.66 ± 1.164) treated group of hamsters. To conclude, f-Comp-AmB could be a safe and reliable therapeutic option over the other carbon-based nanoparticles (NPs), i.e., f-CNT-AmB, f-Grap-AmB, and conventional AmB.</description><subject>antileishmanial activity</subject><subject>Chemistry</subject><subject>cytotoxicity</subject><subject>graphene-CNT composite</subject><subject>nanoparticles</subject><subject>visceral leishmaniasis</subject><issn>2296-2646</issn><issn>2296-2646</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVks1q3DAUhU1paUKafVdFL-Cpfixb7qIwGSZtILSFBLoU1_qJFWzJyJqB6Tv1HSvPpCFZ6UpX5zu66BTFR4JXjIn2s1W9GVcUU7zCmBP8pjintK1LWlf12xf1WXE5z48YY0IJqyh-X5wx2pC2afB58Xe7h2EHyQWPgkV3YE06IPAarX1yg3FzP4J3MKCttU6BOizX1qPzBl3vvFqEMLg_RqMNxC748grmZRPGKcwuGfQDfJggJqcGg9bTZLzO_d8u9Rkz9SGZ6JTz6OpLtkS52LsUw_EJv6JRg_PZdkB3aacPH4p3FobZXD6tF8X99fZ-8728_fntZrO-LRXLU5XAeFd1LaO8JZWwVgCrOGjglWWKK9O0hFvKSK2sEAYIF4Jgy6iyxghu2UVxc8LqAI9yim6EeJABnDwehPggnwaSSpCugwzM-EoLK7oa665rtKCG2EZn1tcTa9p1o9HK-BRheAV93fGulw9hLxvGcctYBuATQMUwz9HYZy3BcgmCPAZBLkGQxyBkyaeXns-C_9_O_gFHirRR</recordid><startdate>20200703</startdate><enddate>20200703</enddate><creator>Gedda, Mallikarjuna Rao</creator><creator>Madhukar, Prasoon</creator><creator>Vishwakarma, Alok Kumar</creator><creator>Verma, Vimal</creator><creator>Kushwaha, Anurag Kumar</creator><creator>Yadagiri, Ganesh</creator><creator>Mudavath, Shyam Lal</creator><creator>Singh, Om Prakash</creator><creator>Srivastava, Onkar Nath</creator><creator>Sundar, Shyam</creator><general>Frontiers Media S.A</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20200703</creationdate><title>Evaluation of Safety and Antileishmanial Efficacy of Amine Functionalized Carbon-Based Composite Nanoparticle Appended With Amphotericin B: An in vitro and Preclinical Study</title><author>Gedda, Mallikarjuna Rao ; Madhukar, Prasoon ; Vishwakarma, Alok Kumar ; Verma, Vimal ; Kushwaha, Anurag Kumar ; Yadagiri, Ganesh ; Mudavath, Shyam Lal ; Singh, Om Prakash ; Srivastava, Onkar Nath ; Sundar, Shyam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3770-a35b4b93259148ff8a345ada54f3c5ce7915f2316cf88ea158810f32cfee85f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>antileishmanial activity</topic><topic>Chemistry</topic><topic>cytotoxicity</topic><topic>graphene-CNT composite</topic><topic>nanoparticles</topic><topic>visceral leishmaniasis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gedda, Mallikarjuna Rao</creatorcontrib><creatorcontrib>Madhukar, Prasoon</creatorcontrib><creatorcontrib>Vishwakarma, Alok Kumar</creatorcontrib><creatorcontrib>Verma, Vimal</creatorcontrib><creatorcontrib>Kushwaha, Anurag Kumar</creatorcontrib><creatorcontrib>Yadagiri, Ganesh</creatorcontrib><creatorcontrib>Mudavath, Shyam Lal</creatorcontrib><creatorcontrib>Singh, Om Prakash</creatorcontrib><creatorcontrib>Srivastava, Onkar Nath</creatorcontrib><creatorcontrib>Sundar, Shyam</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Frontiers in chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gedda, Mallikarjuna Rao</au><au>Madhukar, Prasoon</au><au>Vishwakarma, Alok Kumar</au><au>Verma, Vimal</au><au>Kushwaha, Anurag Kumar</au><au>Yadagiri, Ganesh</au><au>Mudavath, Shyam Lal</au><au>Singh, Om Prakash</au><au>Srivastava, Onkar Nath</au><au>Sundar, Shyam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of Safety and Antileishmanial Efficacy of Amine Functionalized Carbon-Based Composite Nanoparticle Appended With Amphotericin B: An in vitro and Preclinical Study</atitle><jtitle>Frontiers in chemistry</jtitle><addtitle>Front Chem</addtitle><date>2020-07-03</date><risdate>2020</risdate><volume>8</volume><spage>510</spage><pages>510-</pages><issn>2296-2646</issn><eissn>2296-2646</eissn><abstract>Visceral leishmaniasis (VL) has been a major health concern in the developing world, primarily affecting impoverished people. It is caused by a protozoan parasite
and is characterized by immune dysfunction that can lead to deadly secondary infections. Several adverse side effects limit the existing treatment options; hence, the need of the hour is some drug option with high efficacy and no toxicity. To make targeted delivery of Amphotericin B (AmB), we have used amine-functionalized versions of carbon nanostructures, namely f-CNT and f-Graphene (f-Grap). The results with f-Grap-AmB, because of a much larger surface area, were expected to be better. However, the results obtained by us showed only marginal improvement (IC50 f-Grap-AmB; 0.0038 ± 0.00119 μg/mL). This is, in all likelihood, due to the agglomeration effect of f-Grap-AmB, which is invariably obtained with graphene. To resolve this issue, we have synthesized a graphene-CNT composite (graphene 70% and CNT 30% by weight). Because CNT is dispersed in between graphene sheets, the agglomeration effect is avoided, and our study suggests that the f-Composite-AmB (f-Comp-AmB) showed no toxicity against the murine J774A.1 macrophage cell line and did not induce any hepatic or renal toxicity in Swiss albino mice. The f-Comp-AmB also showed a remarkable elevation in the
and
antileishmanial efficacy in comparison to AmB and f-CNT-AmB or f-Grap-AmB in J774A.1 and Golden Syrian hamsters, respectively. Additionally, we have also observed that the percentage suppression of parasite replication in the spleen of the hamster was significantly higher in the f-Comp-AmB (97.79 ± 0.2375) treated group in comparison with the AmB (85.66 ± 1.164) treated group of hamsters. To conclude, f-Comp-AmB could be a safe and reliable therapeutic option over the other carbon-based nanoparticles (NPs), i.e., f-CNT-AmB, f-Grap-AmB, and conventional AmB.</abstract><cop>Switzerland</cop><pub>Frontiers Media S.A</pub><pmid>32719770</pmid><doi>10.3389/fchem.2020.00510</doi><oa>free_for_read</oa></addata></record> |
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subjects | antileishmanial activity Chemistry cytotoxicity graphene-CNT composite nanoparticles visceral leishmaniasis |
title | Evaluation of Safety and Antileishmanial Efficacy of Amine Functionalized Carbon-Based Composite Nanoparticle Appended With Amphotericin B: An in vitro and Preclinical Study |
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