In vitro and in vivo studies of galactose-modified liver-targeting liposomes

Abstract

Oridonin (ORI) is a bioactive diterpenoid compound extracted from the well known Chinese traditional medicine Rabdosia rubescens. The aim of this study was to prepare ORI loaded liposomes surface-modified with galactose (NOH-ORI-LP) and evaluate their characteristics compared with ORI loaded liposomes (ORI-LP) and ORI solution in vitro and in vivo. The NOH-ORI-LP was prepared by ethanol injection method. The NOH-ORI-LP was characterized by their morphology, particle size, zeta potential and encapsulation efficiency. The concentration of ORI in plasma and tissues at different sampling time points were determined. The liver concentration-time curves of NOH-ORI-LP in mice were determined, and the pharmacokinetic parameters were calculated and compared by statistical analysis. Our data revealed that NOH-ORI-LP has a particle size of about (173 ± 12) nm. The particles exhibit a negative electrical charge (−31.5 ± 1.6 mV), and possess high encapsulation efficiency (94.1 ± 1.2%). There were significantly different parameters of k₁₀ and area under the plasma concentration-time curve (AUC_0−t) between liposomes and solution. The mean residence time (MRT_0−t) in plasma of NOH-ORI-LP was 5.56 times longer than that of solution. Compared with solution, NOH-ORI-LP delivered about 4.28 times higher ORI into liver. Thus, an optimum intravenous galactose-modified liposome formulation for ORI could be developed as an alternative to the commercial ORI preparations.

Keywords::

• Liposomes
• galactose
• oridonin
• pharmacokinetics
• biodistribution
• liver targeting