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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.

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TEM shows morphology of blank LCNPs (A) with internal water channel magnified in (B), AE-LCNPs (F6) (C), AE-PEG-LCNPs (F13) (D) with their flower-like structures and internal water channel appeared in (E). All samples were diluted with distilled water (1:20).Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; TEM, transmission electron microscopy.
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f3-ijn-11-4799: TEM shows morphology of blank LCNPs (A) with internal water channel magnified in (B), AE-LCNPs (F6) (C), AE-PEG-LCNPs (F13) (D) with their flower-like structures and internal water channel appeared in (E). All samples were diluted with distilled water (1:20).Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; TEM, transmission electron microscopy.

Mentions: Morphological examination of the prepared LCNP dispersions was examined using TEM. As shown in Figure 3, all the prepared blank LCNPs (Figure 3A and B), AE-LCNPs (Figure 3C), and AE-PEGylated LCNPs (Figure 3D and E) were in the range of 150–200 nm, thus confirming the results of the measurement of PS by DLS. Several nonuniform spherical nanostructures with internal water channels (magnified in Figure 3B) were clearly distinguished. Both large LCNPs (400–500 nm) and small vesicles, often present in LCNP dispersions, were clearly noticed during TEM micrographs by repeated observation. These findings were not obvious during the measurement of PS using DLS. This could be explained as DLS reflects the intensity-weighted size distribution, whereas these vesicles and large LCNPs constitute only small population so they do not affect the whole size distribution. Micrographs of AE-PEGylated LCNPs (Figure 3E; F13) showed spherical flower-like structures with internal water channel and denser outer layer which also confirm efficient PEGylation.19


Stealth, biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells: in vitro and in vivo studies
TEM shows morphology of blank LCNPs (A) with internal water channel magnified in (B), AE-LCNPs (F6) (C), AE-PEG-LCNPs (F13) (D) with their flower-like structures and internal water channel appeared in (E). All samples were diluted with distilled water (1:20).Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; TEM, transmission electron microscopy.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ijn-11-4799: TEM shows morphology of blank LCNPs (A) with internal water channel magnified in (B), AE-LCNPs (F6) (C), AE-PEG-LCNPs (F13) (D) with their flower-like structures and internal water channel appeared in (E). All samples were diluted with distilled water (1:20).Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; TEM, transmission electron microscopy.
Mentions: Morphological examination of the prepared LCNP dispersions was examined using TEM. As shown in Figure 3, all the prepared blank LCNPs (Figure 3A and B), AE-LCNPs (Figure 3C), and AE-PEGylated LCNPs (Figure 3D and E) were in the range of 150–200 nm, thus confirming the results of the measurement of PS by DLS. Several nonuniform spherical nanostructures with internal water channels (magnified in Figure 3B) were clearly distinguished. Both large LCNPs (400–500 nm) and small vesicles, often present in LCNP dispersions, were clearly noticed during TEM micrographs by repeated observation. These findings were not obvious during the measurement of PS using DLS. This could be explained as DLS reflects the intensity-weighted size distribution, whereas these vesicles and large LCNPs constitute only small population so they do not affect the whole size distribution. Micrographs of AE-PEGylated LCNPs (Figure 3E; F13) showed spherical flower-like structures with internal water channel and denser outer layer which also confirm efficient PEGylation.19

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.


Related in: MedlinePlus