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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.


Chemical structure of AE.Abbreviation: AE, aloe-emodin.
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f1-ijn-11-4799: Chemical structure of AE.Abbreviation: AE, aloe-emodin.

Mentions: Recently, herbal drugs have been emerged as one of the promising approaches for cancer therapy with reduced toxicity. Moreover, evidences have proven that numerous herbal drugs are beneficial in sensitizing conventional chemotherapy, alleviating its side effects, and augmenting the quality of life in patients with cancer. Aloe-emodin (AE) is isolated from either Aloe barbadensis Miller or Rheum palmatum L.1 AE belongs to anthraquinones with a structural formula as illustrated in Figure 1. Various pharmacological activities have been demonstrated by AE, including hepatoprotective, antioxidative, antimicrobial, and immunosuppressive activities.2–5 Recently, AE has attracted great attention by virtue of its promising anticancer activity. AE exhibited a remarkable cytotoxic effect against breast, colon, liver, and lung cancer cell lines mediated by different mechanisms of action including cell cycle disruption, apoptotic, anti-angiogenic, anti-metastatic, and immunostimulant action.6


Stealth, biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells: in vitro and in vivo studies
Chemical structure of AE.Abbreviation: AE, aloe-emodin.
© Copyright Policy
Related In: Results  -  Collection

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

f1-ijn-11-4799: Chemical structure of AE.Abbreviation: AE, aloe-emodin.
Mentions: Recently, herbal drugs have been emerged as one of the promising approaches for cancer therapy with reduced toxicity. Moreover, evidences have proven that numerous herbal drugs are beneficial in sensitizing conventional chemotherapy, alleviating its side effects, and augmenting the quality of life in patients with cancer. Aloe-emodin (AE) is isolated from either Aloe barbadensis Miller or Rheum palmatum L.1 AE belongs to anthraquinones with a structural formula as illustrated in Figure 1. Various pharmacological activities have been demonstrated by AE, including hepatoprotective, antioxidative, antimicrobial, and immunosuppressive activities.2–5 Recently, AE has attracted great attention by virtue of its promising anticancer activity. AE exhibited a remarkable cytotoxic effect against breast, colon, liver, and lung cancer cell lines mediated by different mechanisms of action including cell cycle disruption, apoptotic, anti-angiogenic, anti-metastatic, and immunostimulant action.6

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.