Modification of sodium aescinate into a safer, more stable and effective water-soluble drug by liposome-encapsulation: an in vitro and in vivo study

Abstract

Sodium aescinate (SA) is often used for intravenous (IV) injection owing to its anti-inflammatory, anti-exudative, increasing venous tension, improving blood circulation and reducing swelling activities. However, the clinical application of SA is limited by strong irritation, short half-life and low bioavailability. To overcome these defects, we intended to modify SA by encapsualing it with liposomes. SA was mixed with a proper amount of phospholipid and lyophilized to prepare the liposome of sodium aescinate for injection (SA-Lip-I). Its physical properties, cumulative release and dilution stability were evaluated in vitro. Its pharmacodynamic characteristics were evaluated. Safety of SA-Lip-I was evaluated in terms of hemolysis, IV irritation and acute toxicity. The mean particle size of SA-Lip-I was 117.33±0.95 nm, polydispersity index (PDI) was 0.140±0.017, Zeta potential was -30.34±0.23 mv, The cumulative release of SA-Lip at 12 h was more than 80%, which met the release requirements of nanoparticles. SA-Lip-I was well stable in the four mediators and met the clinical medication requirements. In addition, SA-Lip-I had better efficacy than the SA-I and has a significant difference. Furthermore, SA-Lip-I did not induce hemolysis at 37°C, and produced by far milder venous irritation as compared with SA-I. In addition, LD50 of SA-Lip-I was 2.12 fold that of the commercial SA-I, with no obvious side effects.The modified SA-Lip-I is a promising preparation which can reduce the irritation and toxic side effects, improve the treatment effect to a certain extent, but greatly alleviate pain of the patient during treatment, achieving the optimal curative effect.