Stealth, biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells: in vitro and in vivo studies

Abstract

Recently, research has progressively highlighted on clues from conventional use of herbal medicines to introduce new anticancer drugs. Aloe-emodin (AE) is a herbal drug with promising anticancer activity. Nevertheless, its clinical utility is handicapped by its low solubility. For the first time, this study aims to the fabrication of surface-functionalized polyethylene glycol liquid crystalline nanoparticles (PEG-LCNPs) of AE to enhance its water solubility and enable its anticancer use. Developed AE-PEG-LCNPs were optimized via particle size and zeta potential measurements. Phase behavior, solid state characteristics, hemocompatibility, and serum stability of LCNPs were assessed. Sterile formulations were developed using various sterilization technologies. Furthermore, the potential of the formulations was investigated using cell culture, pharmacokinetics, biodistribution, and toxicity studies. AE-PEG-LCNPs showed particle size of 190 nm and zeta potential of −49.9, and PEGylation approach reduced the monoolein hemolytic tendency to 3% and increased the serum stability of the nanoparticles. Sterilization of liquid and lyophilized AE-PEG-LCNPs via autoclaving and γ-radiations, respectively, insignificantly affected the physicochemical properties of the nanoparticles. Half maximal inhibitory concentration of AE-PEG-LCNPs was 3.6-fold lower than free AE after 48 hours and their cellular uptake was threefold higher than free AE after 24-hour incubation. AE-PEG-LCNPs presented 5.4-fold increase in t_1/2 compared with free AE. Biodistribution and toxicity studies showed reduced AE-PEG-LCNP uptake by reticuloendothelial system organs and good safety profile. PEGylated LCNPs could serve as a promising nanocarrier for efficient delivery of AE to cancerous cells.

Keywords:

• aloe-emodin
• anticancer
• breast cancer cell line
• liquid crystalline nanoparticles
• monoolein
• pharmacokinetics

Supplementary material

Lyophilization of liquid crystalline nanoparticle formulations

The optimized dispersions of aloe-emodin (AE)-liquid crystalline nanoparticles (LCNPs) and AE-PEGylated LCNPs were lyophilized in a Cryodos-50 lyophilizer (Telstar Cryodos, Terrassa, Spain) with a condenser temperature of −70°C. Briefly, 25 mL of AE-LCNP dispersions contained 5% w/v mannitol as a cryoprotectant was filled in 50 mL glass vials and subjected to freeze-drying. Lyophilization was performed at a pressure of 40 mbar and a temperature of −40°C for 1 day. The lyophilized AE-LCNPs (yield 90.4% w/w) were stored in a desiccator over P₂O₅ at 25°C until testing. Lyophilized formulations were evaluated for particle size, ζ-potential, polydispersity index, re-dispersibility, and encapsulation efficiency after reconstitution.

Table S1 Physicochemical properties of freeze-dried AE-LCNPs and AE-PEGylated LCNPs

Disclosure

The authors report no conflicts of interest in this work.