title: Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication.
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.
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: K R
authors: KR
authors: Jyothi
authors: Department of Bioengineering and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, Republic of Korea.
authors: Jagadish
authors: J
authors: Beloor
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Ara
authors: A
authors: Jo
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Minh Nam
authors: MN
authors: Nguyen
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Tae Gyu
authors: TG
authors: Choi
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Jin-Hwan
authors: JH
authors: Kim
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Salima
authors: S
authors: Akter
authors: Department of Bioengineering and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, Republic of Korea.
authors: Sang-Kyung
authors: SK
authors: Lee
authors: Department of Medical Oncology and Hematology, Kyung Hee University Hospital, Seoul, Republic of Korea.
authors: Chi Hoon
authors: CH
authors: Maeng
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Hyung Hwan
authors: HH
authors: Baik
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Insug
authors: I
authors: Kang
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Joohun
authors: J
authors: Ha
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Sung Soo
authors: SS
authors: Kim
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016572:Cyclosporine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000821:virology; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016572:Cyclosporine
keywords: HCV; liver-targeting peptide; targeted drug delivery