Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication

KR Jyothi,1 Jagadish Beloor,2 Ara Jo,1 Minh Nam Nguyen,1 Tae Gyu Choi,1 Jin-Hwan Kim,1 Salima Akter,1 Sang-Kyung Lee,2 Chi Hoon Maeng,3 Hyung Hwan Baik,1 Insug Kang,1 Joohun Ha,1 Sung Soo Kim1 1Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seou...

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Autores principales:	Jyothi KR, Beloor J, Jo A, Nguyen MN, Choi TG, Kim JH, Akter S, Lee SK, Maeng CH, Baik HH, Kang I, Ha J, Kim SS
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e007f14725b64c34ba3ab92346a8ba78
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spelling	oai:doaj.org-article:e007f14725b64c34ba3ab92346a8ba782021-12-02T03:11:45ZLiver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication1178-2013https://doaj.org/article/e007f14725b64c34ba3ab92346a8ba782015-01-01T00:00:00Zhttp://www.dovepress.com/liver-targeted-cyclosporine-a-encapsulated-poly-lactic-co-glycolic-aci-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 KR Jyothi,1 Jagadish Beloor,2 Ara Jo,1 Minh Nam Nguyen,1 Tae Gyu Choi,1 Jin-Hwan Kim,1 Salima Akter,1 Sang-Kyung Lee,2 Chi Hoon Maeng,3 Hyung Hwan Baik,1 Insug Kang,1 Joohun Ha,1 Sung Soo Kim1 1Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; 2Department of Bioengineering and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, Republic of Korea; 3Department of Medical Oncology and Hematology, Kyung Hee University Hospital, Seoul, Republic of Korea Abstract: Therapeutic options for hepatitis C virus (HCV) infection have been limited by drug resistance and adverse side effects. Targeting the host factor cyclophilin A (CypA), which is essential for HCV replication, offers a promising strategy for antiviral therapy. However, due to its immunosuppressive activity and severe side effects, clinical application of cyclosporine A (CsA) has been limited as an antiviral agent. To overcome these drawbacks, we have successfully developed a liver-specific, sustained drug delivery system by conjugating the liver-targeting peptide (LTP) to PEGylated CsA-encapsulated poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Furthermore, our delivery system exhibited high specificity to liver, thus contributing to the reduced immunosuppressive effect and toxicity profile of CsA. Finally, targeted nanoparticles were able to effectively inhibit viral replication in vitro and in an HCV mouse model. As a proof of principle, we herein show that our delivery system is able to negate the adverse effects of CsA and produce therapeutic effects in an HCV mouse model.Keywords: HCV, liver-targeting peptide, targeted drug deliveryJyothi KRBeloor JJo ANguyen MNChoi TGKim JHAkter SLee SKMaeng CHBaik HHKang IHa JKim SSDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 903-921 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Jyothi KR Beloor J Jo A Nguyen MN Choi TG Kim JH Akter S Lee SK Maeng CH Baik HH Kang I Ha J Kim SS Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication
description	KR Jyothi,1 Jagadish Beloor,2 Ara Jo,1 Minh Nam Nguyen,1 Tae Gyu Choi,1 Jin-Hwan Kim,1 Salima Akter,1 Sang-Kyung Lee,2 Chi Hoon Maeng,3 Hyung Hwan Baik,1 Insug Kang,1 Joohun Ha,1 Sung Soo Kim1 1Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; 2Department of Bioengineering and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, Republic of Korea; 3Department of Medical Oncology and Hematology, Kyung Hee University Hospital, Seoul, Republic of Korea Abstract: Therapeutic options for hepatitis C virus (HCV) infection have been limited by drug resistance and adverse side effects. Targeting the host factor cyclophilin A (CypA), which is essential for HCV replication, offers a promising strategy for antiviral therapy. However, due to its immunosuppressive activity and severe side effects, clinical application of cyclosporine A (CsA) has been limited as an antiviral agent. To overcome these drawbacks, we have successfully developed a liver-specific, sustained drug delivery system by conjugating the liver-targeting peptide (LTP) to PEGylated CsA-encapsulated poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Furthermore, our delivery system exhibited high specificity to liver, thus contributing to the reduced immunosuppressive effect and toxicity profile of CsA. Finally, targeted nanoparticles were able to effectively inhibit viral replication in vitro and in an HCV mouse model. As a proof of principle, we herein show that our delivery system is able to negate the adverse effects of CsA and produce therapeutic effects in an HCV mouse model.Keywords: HCV, liver-targeting peptide, targeted drug delivery
format	article
author	Jyothi KR Beloor J Jo A Nguyen MN Choi TG Kim JH Akter S Lee SK Maeng CH Baik HH Kang I Ha J Kim SS
author_facet	Jyothi KR Beloor J Jo A Nguyen MN Choi TG Kim JH Akter S Lee SK Maeng CH Baik HH Kang I Ha J Kim SS
author_sort	Jyothi KR
title	Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication
title_short	Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication
title_full	Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication
title_fullStr	Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication
title_full_unstemmed	Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication
title_sort	liver-targeted cyclosporine a-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis c virus replication
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/e007f14725b64c34ba3ab92346a8ba78
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Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication

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