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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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(A) %Hemolysis of blank LCNPs, AE-LCNPs (F6), and AE-PEGylated LCNPs with 1% w/v mPEG2KDSPE (F13) after 0.5-hour and 2-hour incubation period at 37°C. (B) Hemocompatibility profile of AE-PEGylated LCNPs with 2% w/v mPEG2KDSPE (a), AE-PEGylated LCNPs with 1% w/v mPEG2KDSPE (b), AE-PEGylated LCNPs with 0.5% w/v mPEG2KDSPE (c), AE-LCNPs (d) after 2-hour incubation period at 37°C. Changes in both PS (C) and PDI (D) of LCNP formulations after incubation in 10% FBS solution at 37°C.Abbreviations: AE, aloe-emodin; FBS, fetal bovine serum; LCNPs, liquid crystalline nanoparticles; PDI, polydispersity index; PEG, polyethylene glycol; PS, particle size.
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f5-ijn-11-4799: (A) %Hemolysis of blank LCNPs, AE-LCNPs (F6), and AE-PEGylated LCNPs with 1% w/v mPEG2KDSPE (F13) after 0.5-hour and 2-hour incubation period at 37°C. (B) Hemocompatibility profile of AE-PEGylated LCNPs with 2% w/v mPEG2KDSPE (a), AE-PEGylated LCNPs with 1% w/v mPEG2KDSPE (b), AE-PEGylated LCNPs with 0.5% w/v mPEG2KDSPE (c), AE-LCNPs (d) after 2-hour incubation period at 37°C. Changes in both PS (C) and PDI (D) of LCNP formulations after incubation in 10% FBS solution at 37°C.Abbreviations: AE, aloe-emodin; FBS, fetal bovine serum; LCNPs, liquid crystalline nanoparticles; PDI, polydispersity index; PEG, polyethylene glycol; PS, particle size.

Mentions: MO-induced hemolytic property was assessed when incorporated into LCNPs and PEGylated LCNPs via calculating the percentage of RBC lysis. As shown in Figure 5A, blank LCNPs induced relatively low hemolysis tendency (10.72%±3.14%) after 0.5 hours with no significant difference from AE-LCNPs (7.32%±2.14%). However, after incubation for 2 hours, both blank LCNPs and AE-LCNPs showed extensive hemolysis 50%±4.34% and 42%±5.13%, respectively. Hemolytic activity of AE-LCNPs and AE-PEGylated LCNPs with different mPEG2kDSPE concentrations is presented in Figure 5B. It is clearly shown that the addition of low concentration of mPEG2kDSPE could significantly decrease the %hemolysis. mPEG2kDSPE (F12; 0.5% w/v) showed 10.5%±2.14% hemolysis after 2 hours, while no tendency for hemolysis was detected for AE-PEGylated LCNPs at both 1% w/v and 2% w/v mPEG2kDSPE (F13 and F14). These results are in good agreement with that obtained by Jain et al,14 who found that the addition of 1.88% w/w mPEG2kDSPE greatly decreased the hemolytic activity of their prepared paclitaxel–LCNPs. It was reported that PEG layer adsorbed on the surface of MO-LCNPs prevents their interactions with RBCs and subsequent hemolysis.14 Formulated AE-PEGylated LCNPs (F13) were then proposed for systemic administration as it showed only 2%–3% hemolysis, which is less than the accepted nontoxic ratio (5%).


Stealth, biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells: in vitro and in vivo studies
(A) %Hemolysis of blank LCNPs, AE-LCNPs (F6), and AE-PEGylated LCNPs with 1% w/v mPEG2KDSPE (F13) after 0.5-hour and 2-hour incubation period at 37°C. (B) Hemocompatibility profile of AE-PEGylated LCNPs with 2% w/v mPEG2KDSPE (a), AE-PEGylated LCNPs with 1% w/v mPEG2KDSPE (b), AE-PEGylated LCNPs with 0.5% w/v mPEG2KDSPE (c), AE-LCNPs (d) after 2-hour incubation period at 37°C. Changes in both PS (C) and PDI (D) of LCNP formulations after incubation in 10% FBS solution at 37°C.Abbreviations: AE, aloe-emodin; FBS, fetal bovine serum; LCNPs, liquid crystalline nanoparticles; PDI, polydispersity index; PEG, polyethylene glycol; PS, particle size.
© Copyright Policy
Related In: Results  -  Collection

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

f5-ijn-11-4799: (A) %Hemolysis of blank LCNPs, AE-LCNPs (F6), and AE-PEGylated LCNPs with 1% w/v mPEG2KDSPE (F13) after 0.5-hour and 2-hour incubation period at 37°C. (B) Hemocompatibility profile of AE-PEGylated LCNPs with 2% w/v mPEG2KDSPE (a), AE-PEGylated LCNPs with 1% w/v mPEG2KDSPE (b), AE-PEGylated LCNPs with 0.5% w/v mPEG2KDSPE (c), AE-LCNPs (d) after 2-hour incubation period at 37°C. Changes in both PS (C) and PDI (D) of LCNP formulations after incubation in 10% FBS solution at 37°C.Abbreviations: AE, aloe-emodin; FBS, fetal bovine serum; LCNPs, liquid crystalline nanoparticles; PDI, polydispersity index; PEG, polyethylene glycol; PS, particle size.
Mentions: MO-induced hemolytic property was assessed when incorporated into LCNPs and PEGylated LCNPs via calculating the percentage of RBC lysis. As shown in Figure 5A, blank LCNPs induced relatively low hemolysis tendency (10.72%±3.14%) after 0.5 hours with no significant difference from AE-LCNPs (7.32%±2.14%). However, after incubation for 2 hours, both blank LCNPs and AE-LCNPs showed extensive hemolysis 50%±4.34% and 42%±5.13%, respectively. Hemolytic activity of AE-LCNPs and AE-PEGylated LCNPs with different mPEG2kDSPE concentrations is presented in Figure 5B. It is clearly shown that the addition of low concentration of mPEG2kDSPE could significantly decrease the %hemolysis. mPEG2kDSPE (F12; 0.5% w/v) showed 10.5%±2.14% hemolysis after 2 hours, while no tendency for hemolysis was detected for AE-PEGylated LCNPs at both 1% w/v and 2% w/v mPEG2kDSPE (F13 and F14). These results are in good agreement with that obtained by Jain et al,14 who found that the addition of 1.88% w/w mPEG2kDSPE greatly decreased the hemolytic activity of their prepared paclitaxel–LCNPs. It was reported that PEG layer adsorbed on the surface of MO-LCNPs prevents their interactions with RBCs and subsequent hemolysis.14 Formulated AE-PEGylated LCNPs (F13) were then proposed for systemic administration as it showed only 2%–3% hemolysis, which is less than the accepted nontoxic ratio (5%).

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