In vitro susceptibilities of wild and drug resistant leishmania donovani amastigote stages to andrographolide nanoparticle: role of vitamin E derivative TPGS for nanoparticle efficacy
Visceral leishmaniasis (VL) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. There is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need,...
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| Veröffentlicht in: | PloS one 2013-12, Vol.8 (12), p.e81492 |
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| creator | Mondal, Subhasish Roy, Partha Das, Suvadra Halder, Asim Mukherjee, Arup Bera, Tanmoy |
| description | Visceral leishmaniasis (VL) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. There is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need, andrographolide (AG) nanoparticles were designed with P-gp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant Leishmania strains. AG loaded PLGA (50∶50) nanoparticles (AGnps) stabilized by vitamin E TPGS were prepared for delivery into macrophage cells infested with sensitive and drug resistant amastigotes of Leishmania parasites. Physico-chemical characterization of AGnps by photon correlation spectroscopy exhibited an average particle size of 179.6 nm, polydispersity index of 0.245 and zeta potential of -37.6 mV. Atomic force microscopy and transmission electron microscopy visualization revealed spherical nanoparticles with smooth surfaces. AGnps displayed sustained AG release up to 288 hours as well as minimal particle aggregation and drug loss even after three months study period. Antileishmanial activity as revealed from selectivity index in wild-type strain was found to be significant for AGnp with TPGS in about one-tenth of the dosage of the free AG and one-third of the dosage of the AGnp without TPGS. Similar observations were also found in case of in vitro generated drug resistant and field isolated resistant strains of Leishmania. Cytotoxicity of AGnp with and without TPGS was significantly less than standard antileishmanial chemotherapeutics like amphotericin B, paromomycin or sodium stibogluconate. Macrophage uptake of AGnps was almost complete within one hour as evident from fluorescent microscopy studies. Thus, based on these observations, it can be concluded that the low-selectivity of AG in in vitro generated drug resistant and field isolated resistant strains was improved in case of AG nanomedicines designed with vitamin E TPGS. |
| doi_str_mv | 10.1371/journal.pone.0081492 |
| format | Article |
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There is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need, andrographolide (AG) nanoparticles were designed with P-gp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant Leishmania strains. AG loaded PLGA (50∶50) nanoparticles (AGnps) stabilized by vitamin E TPGS were prepared for delivery into macrophage cells infested with sensitive and drug resistant amastigotes of Leishmania parasites. Physico-chemical characterization of AGnps by photon correlation spectroscopy exhibited an average particle size of 179.6 nm, polydispersity index of 0.245 and zeta potential of -37.6 mV. Atomic force microscopy and transmission electron microscopy visualization revealed spherical nanoparticles with smooth surfaces. AGnps displayed sustained AG release up to 288 hours as well as minimal particle aggregation and drug loss even after three months study period. Antileishmanial activity as revealed from selectivity index in wild-type strain was found to be significant for AGnp with TPGS in about one-tenth of the dosage of the free AG and one-third of the dosage of the AGnp without TPGS. Similar observations were also found in case of in vitro generated drug resistant and field isolated resistant strains of Leishmania. Cytotoxicity of AGnp with and without TPGS was significantly less than standard antileishmanial chemotherapeutics like amphotericin B, paromomycin or sodium stibogluconate. Macrophage uptake of AGnps was almost complete within one hour as evident from fluorescent microscopy studies. Thus, based on these observations, it can be concluded that the low-selectivity of AG in in vitro generated drug resistant and field isolated resistant strains was improved in case of AG nanomedicines designed with vitamin E TPGS.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0081492</identifier><identifier>PMID: 24339938</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amastigotes ; Amphotericin B ; Animals ; Atomic force microscopy ; Biochemistry ; Biological Transport - drug effects ; Capsules ; Chemotherapy ; Chronic infection ; Cytotoxicity ; Diterpenes - chemistry ; Diterpenes - metabolism ; Diterpenes - pharmacology ; Dosage ; Drug delivery systems ; Drug Interactions ; Drug resistance ; Drug Resistance - drug effects ; Drug Stability ; Drugs ; Efflux ; Electron microscopy ; Enzymes ; Female ; Fluorescence ; Glycoproteins ; Health aspects ; Kinetics ; Lactic Acid - chemistry ; Leishmania ; Leishmania donovani ; Leishmania donovani - drug effects ; Leishmania donovani - growth & development ; Leishmaniasis ; Load resistance ; Localization ; Macrophages ; Male ; Mice ; Mice, Inbred BALB C ; Microscopy ; Morbidity ; Nanoparticles ; Nanoparticles - chemistry ; Parasites ; Parasitic diseases ; Paromomycin ; Particle Size ; Pharmaceutical sciences ; Photon correlation spectroscopy ; Polydispersity ; Polyethylene glycol ; Polyethylene Glycols - pharmacology ; Polyglycolic Acid - chemistry ; Polylactide-co-glycolide ; Polyvinyl alcohol ; Proteins ; Protozoa ; Selectivity ; Sodium ; Sodium stibogluconate ; Spectroscopy ; Tocopherol ; Toxicity ; Transmission electron microscopy ; Tropical diseases ; Vector-borne diseases ; Visceral leishmaniasis ; Vitamin E ; Vitamin E - analogs & derivatives ; Vitamin E - pharmacology ; Zeta potential</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e81492</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Mondal et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Mondal et al 2013 Mondal et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-5ebaa37addd531908c35ec2253fcbdb18097a9011b50df3aee831f4056db43ac3</citedby><cites>FETCH-LOGICAL-c692t-5ebaa37addd531908c35ec2253fcbdb18097a9011b50df3aee831f4056db43ac3</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/PMC3858255/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858255/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,2098,2917,23849,27907,27908,53774,53776,79351,79352</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24339938$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Satoskar, Abhay R.</contributor><creatorcontrib>Mondal, Subhasish</creatorcontrib><creatorcontrib>Roy, Partha</creatorcontrib><creatorcontrib>Das, Suvadra</creatorcontrib><creatorcontrib>Halder, Asim</creatorcontrib><creatorcontrib>Mukherjee, Arup</creatorcontrib><creatorcontrib>Bera, Tanmoy</creatorcontrib><title>In vitro susceptibilities of wild and drug resistant leishmania donovani amastigote stages to andrographolide nanoparticle: role of vitamin E derivative TPGS for nanoparticle efficacy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Visceral leishmaniasis (VL) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. There is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need, andrographolide (AG) nanoparticles were designed with P-gp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant Leishmania strains. AG loaded PLGA (50∶50) nanoparticles (AGnps) stabilized by vitamin E TPGS were prepared for delivery into macrophage cells infested with sensitive and drug resistant amastigotes of Leishmania parasites. Physico-chemical characterization of AGnps by photon correlation spectroscopy exhibited an average particle size of 179.6 nm, polydispersity index of 0.245 and zeta potential of -37.6 mV. Atomic force microscopy and transmission electron microscopy visualization revealed spherical nanoparticles with smooth surfaces. AGnps displayed sustained AG release up to 288 hours as well as minimal particle aggregation and drug loss even after three months study period. Antileishmanial activity as revealed from selectivity index in wild-type strain was found to be significant for AGnp with TPGS in about one-tenth of the dosage of the free AG and one-third of the dosage of the AGnp without TPGS. Similar observations were also found in case of in vitro generated drug resistant and field isolated resistant strains of Leishmania. Cytotoxicity of AGnp with and without TPGS was significantly less than standard antileishmanial chemotherapeutics like amphotericin B, paromomycin or sodium stibogluconate. Macrophage uptake of AGnps was almost complete within one hour as evident from fluorescent microscopy studies. Thus, based on these observations, it can be concluded that the low-selectivity of AG in in vitro generated drug resistant and field isolated resistant strains was improved in case of AG nanomedicines designed with vitamin E TPGS.</description><subject>Amastigotes</subject><subject>Amphotericin B</subject><subject>Animals</subject><subject>Atomic force microscopy</subject><subject>Biochemistry</subject><subject>Biological Transport - drug effects</subject><subject>Capsules</subject><subject>Chemotherapy</subject><subject>Chronic infection</subject><subject>Cytotoxicity</subject><subject>Diterpenes - chemistry</subject><subject>Diterpenes - metabolism</subject><subject>Diterpenes - pharmacology</subject><subject>Dosage</subject><subject>Drug delivery systems</subject><subject>Drug Interactions</subject><subject>Drug resistance</subject><subject>Drug Resistance - drug effects</subject><subject>Drug Stability</subject><subject>Drugs</subject><subject>Efflux</subject><subject>Electron microscopy</subject><subject>Enzymes</subject><subject>Female</subject><subject>Fluorescence</subject><subject>Glycoproteins</subject><subject>Health aspects</subject><subject>Kinetics</subject><subject>Lactic Acid - chemistry</subject><subject>Leishmania</subject><subject>Leishmania donovani</subject><subject>Leishmania donovani - drug effects</subject><subject>Leishmania donovani - growth & development</subject><subject>Leishmaniasis</subject><subject>Load resistance</subject><subject>Localization</subject><subject>Macrophages</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microscopy</subject><subject>Morbidity</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Paromomycin</subject><subject>Particle Size</subject><subject>Pharmaceutical sciences</subject><subject>Photon correlation spectroscopy</subject><subject>Polydispersity</subject><subject>Polyethylene glycol</subject><subject>Polyethylene Glycols - pharmacology</subject><subject>Polyglycolic Acid - chemistry</subject><subject>Polylactide-co-glycolide</subject><subject>Polyvinyl alcohol</subject><subject>Proteins</subject><subject>Protozoa</subject><subject>Selectivity</subject><subject>Sodium</subject><subject>Sodium stibogluconate</subject><subject>Spectroscopy</subject><subject>Tocopherol</subject><subject>Toxicity</subject><subject>Transmission electron microscopy</subject><subject>Tropical diseases</subject><subject>Vector-borne diseases</subject><subject>Visceral leishmaniasis</subject><subject>Vitamin E</subject><subject>Vitamin E - 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chemistry</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Paromomycin</topic><topic>Particle Size</topic><topic>Pharmaceutical sciences</topic><topic>Photon correlation spectroscopy</topic><topic>Polydispersity</topic><topic>Polyethylene glycol</topic><topic>Polyethylene Glycols - pharmacology</topic><topic>Polyglycolic Acid - chemistry</topic><topic>Polylactide-co-glycolide</topic><topic>Polyvinyl alcohol</topic><topic>Proteins</topic><topic>Protozoa</topic><topic>Selectivity</topic><topic>Sodium</topic><topic>Sodium stibogluconate</topic><topic>Spectroscopy</topic><topic>Tocopherol</topic><topic>Toxicity</topic><topic>Transmission electron microscopy</topic><topic>Tropical diseases</topic><topic>Vector-borne diseases</topic><topic>Visceral leishmaniasis</topic><topic>Vitamin E</topic><topic>Vitamin E - analogs & derivatives</topic><topic>Vitamin E - pharmacology</topic><topic>Zeta potential</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mondal, Subhasish</creatorcontrib><creatorcontrib>Roy, Partha</creatorcontrib><creatorcontrib>Das, Suvadra</creatorcontrib><creatorcontrib>Halder, Asim</creatorcontrib><creatorcontrib>Mukherjee, Arup</creatorcontrib><creatorcontrib>Bera, Tanmoy</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mondal, Subhasish</au><au>Roy, Partha</au><au>Das, Suvadra</au><au>Halder, Asim</au><au>Mukherjee, Arup</au><au>Bera, Tanmoy</au><au>Satoskar, Abhay R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro susceptibilities of wild and drug resistant leishmania donovani amastigote stages to andrographolide nanoparticle: role of vitamin E derivative TPGS for nanoparticle efficacy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-12-10</date><risdate>2013</risdate><volume>8</volume><issue>12</issue><spage>e81492</spage><pages>e81492-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Visceral leishmaniasis (VL) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. There is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need, andrographolide (AG) nanoparticles were designed with P-gp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant Leishmania strains. AG loaded PLGA (50∶50) nanoparticles (AGnps) stabilized by vitamin E TPGS were prepared for delivery into macrophage cells infested with sensitive and drug resistant amastigotes of Leishmania parasites. Physico-chemical characterization of AGnps by photon correlation spectroscopy exhibited an average particle size of 179.6 nm, polydispersity index of 0.245 and zeta potential of -37.6 mV. Atomic force microscopy and transmission electron microscopy visualization revealed spherical nanoparticles with smooth surfaces. AGnps displayed sustained AG release up to 288 hours as well as minimal particle aggregation and drug loss even after three months study period. Antileishmanial activity as revealed from selectivity index in wild-type strain was found to be significant for AGnp with TPGS in about one-tenth of the dosage of the free AG and one-third of the dosage of the AGnp without TPGS. Similar observations were also found in case of in vitro generated drug resistant and field isolated resistant strains of Leishmania. Cytotoxicity of AGnp with and without TPGS was significantly less than standard antileishmanial chemotherapeutics like amphotericin B, paromomycin or sodium stibogluconate. Macrophage uptake of AGnps was almost complete within one hour as evident from fluorescent microscopy studies. Thus, based on these observations, it can be concluded that the low-selectivity of AG in in vitro generated drug resistant and field isolated resistant strains was improved in case of AG nanomedicines designed with vitamin E TPGS.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24339938</pmid><doi>10.1371/journal.pone.0081492</doi><tpages>e81492</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-12, Vol.8 (12), p.e81492 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1466544161 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Amastigotes Amphotericin B Animals Atomic force microscopy Biochemistry Biological Transport - drug effects Capsules Chemotherapy Chronic infection Cytotoxicity Diterpenes - chemistry Diterpenes - metabolism Diterpenes - pharmacology Dosage Drug delivery systems Drug Interactions Drug resistance Drug Resistance - drug effects Drug Stability Drugs Efflux Electron microscopy Enzymes Female Fluorescence Glycoproteins Health aspects Kinetics Lactic Acid - chemistry Leishmania Leishmania donovani Leishmania donovani - drug effects Leishmania donovani - growth & development Leishmaniasis Load resistance Localization Macrophages Male Mice Mice, Inbred BALB C Microscopy Morbidity Nanoparticles Nanoparticles - chemistry Parasites Parasitic diseases Paromomycin Particle Size Pharmaceutical sciences Photon correlation spectroscopy Polydispersity Polyethylene glycol Polyethylene Glycols - pharmacology Polyglycolic Acid - chemistry Polylactide-co-glycolide Polyvinyl alcohol Proteins Protozoa Selectivity Sodium Sodium stibogluconate Spectroscopy Tocopherol Toxicity Transmission electron microscopy Tropical diseases Vector-borne diseases Visceral leishmaniasis Vitamin E Vitamin E - analogs & derivatives Vitamin E - pharmacology Zeta potential |
| title | In vitro susceptibilities of wild and drug resistant leishmania donovani amastigote stages to andrographolide nanoparticle: role of vitamin E derivative TPGS for nanoparticle efficacy |
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