Novel polyion complex micelles for liver‐targeted delivery of diammonium glycyrrhizinate: In vitro and in vivo characterization

Abstract

Polyion complex micelles (PIC micelles) based on methoxy poly(ethylene glycol)-grafted-chitosan (mPEG-g-Chitosan) and lactose-conjugated PEG-grafted-chitosan (Lac-PEG-g-Chitosan) were designed as carriers for anionic drugs. Diammonium glycyrrhizinate (DG)-loaded conventional PIC micelles (mPIC micelles) and lactose-modified PIC micelles (Lac-PIC micelles) were prepared successfully with encapsulation efficiency of 97.4% and 96.7%, respectively. These micelles were uniform spherical particles with a mean size of 21.6 and 26.4 nm by transmission electron microscopy, respectively. No significant size change of these micelles in three months indicated their good physical stability. The in vitro drug release behavior of mPIC micelles in different media as well as the changes of size and zeta potential demonstrated that the drug was released mainly through swelling and diffusion induced by ion exchange. The pharmacokinetic experiments showed that the area under the curve of DG plasma concentration-time profile in rats for mPIC micelles and Lac-PIC micelles were 1.2 times and 0.4 times higher than that for DG injection, respectively. The liver targeting ability of both mPIC micelles and Lac-PIC micelles was evaluated in rats, revealing that Lac-PIC micelles could deliver more DG to liver than mPIC micelles. Therefore, the Lac-PIC micelles prepared in this study were promising liver-targeted nanocarriers for DG.

Chitosan Mediated Targeted Drug Delivery System: A Review

“…Recently, Liu et al prepared polyion complex micelles (PIC micelles) based on methoxy poly (ethylene glycol) (PEG)-graftchitosan and lactoseconjugated PEG-graft-chitosan for liver-targeted delivery of diammonium glycyrrhizinate (DG) [46]. DG has been used in the treatment of chronic hepatitis and immunode.ciency virus infection.…”

Influence of the Chemical Structure and Physicochemical Properties of Chitin- and Chitosan-Based Materials on Their Biomedical Activity

“…For example, Kato et al evaluated the potential of lactosaminated N-succinyl-chitosan (Lac-Suc) as a liver-specific drug carrier (Kato et al, 2001). More recently, Yang et al prepared polyion complex micelles (PIC micelles), also for liver-targeted delivery (Yang et al, 2009a). These micelles were based on methoxy poly (ethylene glycol)-graft-chitosan and lactose-conjugated poly (ethylene glycol)-graft-chitosan, and was prepared for the delivery of diammonium glycyrrhizinate (DG).…”

Preparation, characterization, and tissue distribution in mice of lactosaminated carboxymethyl chitosan nanoparticles

“…Galactosylated chitosan-graft-poly (ethylene glycol) (Park et al, 2001), galactosylated chitosan-graft-dextran (Park et al, 2000) and galactosylated chitosan-graft-poly(vinyl pyrrolidone) (Park et al, 2003) as a hepatocyte-targeting DNA carrier were proved to have excellent specificity to liver cells. Recently, Yang et al (2009) prepared lactose-conjugated PEG-graft-chitosan for liver-targeted delivery of diammonium glycyrrhizinate. Due to good water solubility, safe toxicity and excellent biocompatibility of CMC and liver specificity of galactose group, LAC-CMC may lead to a carrier that possesses the effects of inclusion and hepatic targeting properties.…”