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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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Cytotoxicity analysis of free AE, AE-LCNPs, AE-PEGylated LCNPs (F13), and blank LCNPs on MCF-7 cells at the concentration of 5–90 µM after 24 hours (A) and 48 hours (B). Data are represented as mean ± SD (n=3), P<0.05. (C) Cellular uptake amount of free AE, AE-LCNPs (F6), and AE-PEG-LCNPs (F13) by MCF-7 cells at fixed AE concentration of 5 µM within 24 hours. Data are represented as mean ± SD (n=3), P<0.05.Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; SD, standard deviation.
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f6-ijn-11-4799: Cytotoxicity analysis of free AE, AE-LCNPs, AE-PEGylated LCNPs (F13), and blank LCNPs on MCF-7 cells at the concentration of 5–90 µM after 24 hours (A) and 48 hours (B). Data are represented as mean ± SD (n=3), P<0.05. (C) Cellular uptake amount of free AE, AE-LCNPs (F6), and AE-PEG-LCNPs (F13) by MCF-7 cells at fixed AE concentration of 5 µM within 24 hours. Data are represented as mean ± SD (n=3), P<0.05.Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; SD, standard deviation.

Mentions: The cytotoxicity of free AE, AE-LCNPs (F6), AE-PEGylated LCNPs (F13), and blank LCNPs at AE concentration range of 5–90 µM was assessed on human breast cancer cells, MCF-7, using MTT assay. This assay is a quantitative dye-based assay that depends on the metabolic activity of viable cells. In MTT assay, only metabolically active viable cells are able to convert the yellow MTT dye to purple MTT formazan crystals, which are further dissolved in solvent and analyzed spectrophotometrically.44Figure 6A and B shows the cytotoxicity results of blank LCNPs, free AE, AE-LCNPs (F6), and AE-PEGylated LCNPs (F13) after incubation with MCF-7 cells for 24 hours (Figure 6A) and 48 hours (Figure 6B). As shown in Figure 6, both free AE and AE-LCNP dispersions demonstrated considerable reduction in cell viability in a dose- and time-dependent manner. However, at the same concentration, AE-LCNPs showed significantly (P<0.05) higher proliferation inhibitory effects when compared with free AE solution. This could be manifested as lower half maximal inhibitory concentration (IC50) values (50% growth inhibition) compared with free AE solution. The IC50 values of AE-LCNPs were found to be 26 µM and 18 µM following 24-hour and 48-hour incubation, respectively, which was 3.18- and 4.34-fold lower compared with free AE (Table 4). Blank LCNPs did not show remarkable cytotoxicity and maintained cell viability ~90% after both 24 hours and 48 hours, suggesting its cytocompatibility and confirming that the cytotoxicity of AE-LCNPs was due to AE.


Stealth, biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells: in vitro and in vivo studies
Cytotoxicity analysis of free AE, AE-LCNPs, AE-PEGylated LCNPs (F13), and blank LCNPs on MCF-7 cells at the concentration of 5–90 µM after 24 hours (A) and 48 hours (B). Data are represented as mean ± SD (n=3), P<0.05. (C) Cellular uptake amount of free AE, AE-LCNPs (F6), and AE-PEG-LCNPs (F13) by MCF-7 cells at fixed AE concentration of 5 µM within 24 hours. Data are represented as mean ± SD (n=3), P<0.05.Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; SD, standard deviation.
© Copyright Policy
Related In: Results  -  Collection

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

f6-ijn-11-4799: Cytotoxicity analysis of free AE, AE-LCNPs, AE-PEGylated LCNPs (F13), and blank LCNPs on MCF-7 cells at the concentration of 5–90 µM after 24 hours (A) and 48 hours (B). Data are represented as mean ± SD (n=3), P<0.05. (C) Cellular uptake amount of free AE, AE-LCNPs (F6), and AE-PEG-LCNPs (F13) by MCF-7 cells at fixed AE concentration of 5 µM within 24 hours. Data are represented as mean ± SD (n=3), P<0.05.Abbreviations: AE, aloe-emodin; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; SD, standard deviation.
Mentions: The cytotoxicity of free AE, AE-LCNPs (F6), AE-PEGylated LCNPs (F13), and blank LCNPs at AE concentration range of 5–90 µM was assessed on human breast cancer cells, MCF-7, using MTT assay. This assay is a quantitative dye-based assay that depends on the metabolic activity of viable cells. In MTT assay, only metabolically active viable cells are able to convert the yellow MTT dye to purple MTT formazan crystals, which are further dissolved in solvent and analyzed spectrophotometrically.44Figure 6A and B shows the cytotoxicity results of blank LCNPs, free AE, AE-LCNPs (F6), and AE-PEGylated LCNPs (F13) after incubation with MCF-7 cells for 24 hours (Figure 6A) and 48 hours (Figure 6B). As shown in Figure 6, both free AE and AE-LCNP dispersions demonstrated considerable reduction in cell viability in a dose- and time-dependent manner. However, at the same concentration, AE-LCNPs showed significantly (P<0.05) higher proliferation inhibitory effects when compared with free AE solution. This could be manifested as lower half maximal inhibitory concentration (IC50) values (50% growth inhibition) compared with free AE solution. The IC50 values of AE-LCNPs were found to be 26 µM and 18 µM following 24-hour and 48-hour incubation, respectively, which was 3.18- and 4.34-fold lower compared with free AE (Table 4). Blank LCNPs did not show remarkable cytotoxicity and maintained cell viability ~90% after both 24 hours and 48 hours, suggesting its cytocompatibility and confirming that the cytotoxicity of AE-LCNPs was due to AE.

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 &minus;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 &gamma;-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