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

View Article: PubMed Central - PubMed

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 t1/2 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.

No MeSH data available.


Polarized optical microscopy of AE-LCNPs prepared by thin film hydration method (F6-2) (A), blank LCNPs (B), AE-LCNPs (F6) (C), AE-PEGylated LCNPs (F13) (D). (B–D) Prepared by emulsification technique.Note: Magnification ×100.Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol.
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f2-ijn-11-4799: Polarized optical microscopy of AE-LCNPs prepared by thin film hydration method (F6-2) (A), blank LCNPs (B), AE-LCNPs (F6) (C), AE-PEGylated LCNPs (F13) (D). (B–D) Prepared by emulsification technique.Note: Magnification ×100.Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol.

Mentions: MO-based LCNPs and PEGylated system were prepared by emulsification method. In this method, the dispersion of MO/P407 mixtures in water resulted in the formation of supramolecular systems consisted of LC lipidic particles and vesicles in a submicron PS range. Then, the hot dispersion was subjected to brief homogenization for 1 minute to obtain opaque uniform nano-dispersion free from aggregates. A second well-known thin film hydration method was also utilized for the formulation of LCNPs. However, upon using this method, lipid aggregates and AE crystals were observed indicating the failure of this method to efficiently incorporate AE in the lipid matrix. This was confirmed by polarizing microscope photographs (Figure 2A) showing the phase behavior of AE-LCNPs under the polarizing microscope as detailed in the following sections. Consequently, continuing with film hydration was discouraged and emulsification method was adopted for the preparation of AE-LCNPs. It is worth noting that the emulsification method has many advantages, including simplicity and saving of time, in contrast to other drastic and time-consuming conventional methods of preparation.32


Stealth, biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells: in vitro and in vivo studies
Polarized optical microscopy of AE-LCNPs prepared by thin film hydration method (F6-2) (A), blank LCNPs (B), AE-LCNPs (F6) (C), AE-PEGylated LCNPs (F13) (D). (B–D) Prepared by emulsification technique.Note: Magnification ×100.Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5036603&req=5

f2-ijn-11-4799: Polarized optical microscopy of AE-LCNPs prepared by thin film hydration method (F6-2) (A), blank LCNPs (B), AE-LCNPs (F6) (C), AE-PEGylated LCNPs (F13) (D). (B–D) Prepared by emulsification technique.Note: Magnification ×100.Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol.
Mentions: MO-based LCNPs and PEGylated system were prepared by emulsification method. In this method, the dispersion of MO/P407 mixtures in water resulted in the formation of supramolecular systems consisted of LC lipidic particles and vesicles in a submicron PS range. Then, the hot dispersion was subjected to brief homogenization for 1 minute to obtain opaque uniform nano-dispersion free from aggregates. A second well-known thin film hydration method was also utilized for the formulation of LCNPs. However, upon using this method, lipid aggregates and AE crystals were observed indicating the failure of this method to efficiently incorporate AE in the lipid matrix. This was confirmed by polarizing microscope photographs (Figure 2A) showing the phase behavior of AE-LCNPs under the polarizing microscope as detailed in the following sections. Consequently, continuing with film hydration was discouraged and emulsification method was adopted for the preparation of AE-LCNPs. It is worth noting that the emulsification method has many advantages, including simplicity and saving of time, in contrast to other drastic and time-consuming conventional methods of preparation.32

View Article: PubMed Central - PubMed

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 t1/2 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.

No MeSH data available.