Fully biodegradable and cationic poly(amino oxalate) particles for the treatment of acetaminophen-induced acute liver failure.
Acute inflammatory diseases are one of major causes of death in the world and there is great need for developing drug delivery systems that can target drugs to macrophages and enhance their therapeutic efficacy. Poly(amino oxalate) (PAOX) is a new family of fully biodegradable polymer that possesses tertiary amine groups in its backbone and has rapid hydrolytic degradation. In this study, we developed PAOX particles as drug delivery systems for treating acute liver failure (ALF) by taking the advantages of the natural propensity of particulate drug delivery systems to localize to the mononuclear phagocyte system, particularly to liver macrophages. PAOX particles showed a fast drug release kinetics and excellent biocompatibility in vitro and in vivo. A majority of PAOX particles were accumulated in liver, providing a rational strategy for effective treatment of ALF. A mouse model of acetaminophen (APAP)-induced ALF was used to evaluate the potential of PAOX particles using pentoxifylline (PTX) as a model drug. Treatment of PTX-loaded PAOX particles significantly reduced the activity of alanine transaminase (ALT) and inhibited hepatic cell damages in APAP-intoxicated mice. The high therapeutic efficacy of PTX-loaded PAOX particles for ALF treatment may be attributed to the unique properties of PAOX particles, which can target passively liver, stimulate cellular uptake and trigger a colloid osmotic disruption of the phagosome to release encapsulated PTX into the cytosol. Taken together, we believe that PAOX particles are a promising drug delivery candidate for the treatment of acute inflammatory diseases.
Department of BIN Fusion Technology, Chonbuk National University, Jeonju 561-756, Republic of Korea.
Hyungmin
H
Kim
Yerang
Y
Kim
Kyeonghye
K
Guk
Donghyuck
D
Yoo
Hyungsuk
H
Lim
Gilson
G
Kang
Dongwon
D
Lee
D000082:Acetaminophen / Q000633:toxicity*; D000208:Acute Disease; D000818:Animals; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D010070:Oxalates / Q000737:chemistry* / Q000493:pharmacokinetics; D010431:Pentoxifylline / Q000008:administration & dosage* / Q000494:pharmacology; D014018:Tissue Distribution
D004337:Drug Carriers; D010070:Oxalates; D000082:Acetaminophen; D010431:Pentoxifylline