title: Antioxidant polymeric prodrug microparticles as a therapeutic system for acute liver failure.
abstract: Acetaminophen (APAP) is the most widely used analgesic and its overdose, intentional or unintentional, is known to cause massive oxidative stress and liver tissue damages characterized by hepatocellular apoptosis and hemorrhagic necrosis, leading to acute liver failure (ALF). There has been great interest in the use of antioxidant and anti-inflammatory drugs for the effective treatment of ALF. Manganese porphyrin (MnP), a nonpeptidyl mimic of superoxide dismutase is a promising compound with antioxidant activity, but its application is curtailed by a short half-life in blood. We have recently developed a new family of biodegradable and antioxidant polymeric prodrug, poly(vanillyl alcohol-co-oxalate) (PVAX), which is able to scavenge H2O2 and release antioxidant and anti-inflammatory vanillyl alcohol. In this work, we developed MnP-loaded PVAX particles and evaluated their potential as antioxidant and anti-inflammatory therapeutic agents for APAP-induced ALF. PVAX particles and MnP showed synergistic antioxidant and anti-inflammatory activities in macrophages stimulated with LPS (lipopolysaccharide). Animal studies using a mouse model of APAP-induced ALF revealed that MnP-loaded PVAX particles significantly reduced the serum ALT level and protected liver damages. We anticipated that MnP-loaded PVAX particles have great potential as a therapeutic agent for oxidative stress-associated diseases such as APAP-induced ALF.
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea.
authors: Eunbyul
authors: E
authors: Ko
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea.
authors: Dahee
authors: D
authors: Jeong
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea.
authors: Jihye
authors: J
authors: Kim
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea.
authors: Sanga
authors: S
authors: Park
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea; Department of Polymer Nano Science and Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea.
authors: Gilson
authors: G
authors: Khang
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea; Department of Polymer Nano Science and Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea. Electronic address: dlee@chonbuk.ac.kr.
authors: Dongwon
authors: D
authors: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001672:Biocompatible Materials; D002460:Cell Line; D017114:Liver Failure, Acute / Q000188:drug therapy*; D051379:Mice; D011108:Polymers / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011355:Prodrugs / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
chemical_list: D000975:Antioxidants; D001672:Biocompatible Materials; D011108:Polymers; D011355:Prodrugs
keywords: Acute liver failure; Biodegradable polymer; Hydrogen peroxide; Inflammation; Reactive oxygen species