Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis

Muzamil Y Want,1 Mohammad Islammudin,1 Garima Chouhan,1 Hani A Ozbak,2 Hassan A Hemeg,2 Asoke P Chattopadhyay,3 Farhat Afrin2 1Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard, Hamdard University, New Delhi, India; 2Department of Clinical Laboratory Sciences, Faculty of Ap...

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Autores principales:	Want MY, Islamuddin M, Chouhan G, Ozbak HA, Hemeg HA, Chattopadhyay AP, Afrin F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Visceral leishmaniasis Box-Behnken Nanoliposomes Drug delivery Artemisinin Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0fc43d0749864bb5a9372e01e4f423f1
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spelling	oai:doaj.org-article:0fc43d0749864bb5a9372e01e4f423f12021-12-02T02:43:43ZNanoliposomal artemisinin for the treatment of murine visceral leishmaniasis1178-2013https://doaj.org/article/0fc43d0749864bb5a9372e01e4f423f12017-03-01T00:00:00Zhttps://www.dovepress.com/nanoliposomal-artemisinin-for-the-treatment-of-murine-visceral-leishma-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Muzamil Y Want,1 Mohammad Islammudin,1 Garima Chouhan,1 Hani A Ozbak,2 Hassan A Hemeg,2 Asoke P Chattopadhyay,3 Farhat Afrin2 1Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard, Hamdard University, New Delhi, India; 2Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia; 3Department of Chemistry, University of Kalyani, Kalyani, India Abstract: Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA) was prepared by thin-film hydration method and optimized using Box–Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of -27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a percentage inhibition of 82.4%±3.8% in the liver and 77.6%±5.5% in spleen at the highest dose of 20 mg/kg body weight with modulation of cell-mediated immunity towards protective Th1 type. This study is the first report on the use of a liposomal drug delivery system for artemisinin as a promising alternative intervention against VL. Keywords: visceral leishmaniasis, Box–Behnken, nanoliposomes, drug delivery, artemisinin, Leishmania Want MYIslamuddin MChouhan GOzbak HAHemeg HAChattopadhyay APAfrin FDove Medical PressarticleVisceral leishmaniasisBox-BehnkenNanoliposomesDrug deliveryArtemisininMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2189-2204 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Visceral leishmaniasis Box-Behnken Nanoliposomes Drug delivery Artemisinin Medicine (General) R5-920
spellingShingle	Visceral leishmaniasis Box-Behnken Nanoliposomes Drug delivery Artemisinin Medicine (General) R5-920 Want MY Islamuddin M Chouhan G Ozbak HA Hemeg HA Chattopadhyay AP Afrin F Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis
description	Muzamil Y Want,1 Mohammad Islammudin,1 Garima Chouhan,1 Hani A Ozbak,2 Hassan A Hemeg,2 Asoke P Chattopadhyay,3 Farhat Afrin2 1Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard, Hamdard University, New Delhi, India; 2Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia; 3Department of Chemistry, University of Kalyani, Kalyani, India Abstract: Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA) was prepared by thin-film hydration method and optimized using Box–Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of -27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a percentage inhibition of 82.4%±3.8% in the liver and 77.6%±5.5% in spleen at the highest dose of 20 mg/kg body weight with modulation of cell-mediated immunity towards protective Th1 type. This study is the first report on the use of a liposomal drug delivery system for artemisinin as a promising alternative intervention against VL. Keywords: visceral leishmaniasis, Box–Behnken, nanoliposomes, drug delivery, artemisinin, Leishmania
format	article
author	Want MY Islamuddin M Chouhan G Ozbak HA Hemeg HA Chattopadhyay AP Afrin F
author_facet	Want MY Islamuddin M Chouhan G Ozbak HA Hemeg HA Chattopadhyay AP Afrin F
author_sort	Want MY
title	Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis
title_short	Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis
title_full	Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis
title_fullStr	Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis
title_full_unstemmed	Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis
title_sort	nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/0fc43d0749864bb5a9372e01e4f423f1
work_keys_str_mv	AT wantmy nanoliposomalartemisininforthetreatmentofmurinevisceralleishmaniasis AT islamuddinm nanoliposomalartemisininforthetreatmentofmurinevisceralleishmaniasis AT chouhang nanoliposomalartemisininforthetreatmentofmurinevisceralleishmaniasis AT ozbakha nanoliposomalartemisininforthetreatmentofmurinevisceralleishmaniasis AT hemegha nanoliposomalartemisininforthetreatmentofmurinevisceralleishmaniasis AT chattopadhyayap nanoliposomalartemisininforthetreatmentofmurinevisceralleishmaniasis AT afrinf nanoliposomalartemisininforthetreatmentofmurinevisceralleishmaniasis
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Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis

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