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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) DSC thermograms of (a) blank LCNPs, (b) AE-LCNPs (F6), (c) AE-PEGylated LCNPs (F13), and (d) free AE. (B) IR spectra of blank LCNPs, AE-LCNPs (F6), AE-PEGylated LCNPs (F13), and free AE. (C) XRD patterns of free AE (A), blank LCNPs (B), AE-LCNPs (C) (F6), and AE-PEGylated LCNPs (D) (F13). (D) In vitro release study of free AE, AE-LCNPs (F6), and AE-PEGylated LCNPs (F13) in phosphate buffer, pH 7.4; 1% Tween 80 at 75 rpm and 37°C using dialysis bag method.Abbreviations: AE, aloe-emodin; DSC, differential scanning calorimetry; IR, infrared; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; XRD, X-ray powder diffraction.
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f4-ijn-11-4799: (A) DSC thermograms of (a) blank LCNPs, (b) AE-LCNPs (F6), (c) AE-PEGylated LCNPs (F13), and (d) free AE. (B) IR spectra of blank LCNPs, AE-LCNPs (F6), AE-PEGylated LCNPs (F13), and free AE. (C) XRD patterns of free AE (A), blank LCNPs (B), AE-LCNPs (C) (F6), and AE-PEGylated LCNPs (D) (F13). (D) In vitro release study of free AE, AE-LCNPs (F6), and AE-PEGylated LCNPs (F13) in phosphate buffer, pH 7.4; 1% Tween 80 at 75 rpm and 37°C using dialysis bag method.Abbreviations: AE, aloe-emodin; DSC, differential scanning calorimetry; IR, infrared; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; XRD, X-ray powder diffraction.

Mentions: DSC is a common and reliable method used to investigate any change that could be occurred in drug crystallinity during nanoparticle formulation (Figure 4A). The thermogram of AE showed one sharp endothermal peak at 223°C (Figure 4A[d]). DSC of AE-LCNPs (Figure 4A[b]) and AE-PEGylated LCNPs (Figure 4A[c]) showed that the characteristic endothermal peak of the drug disappeared indicating that the encapsulated AE in LCNPs was converted to its amorphous state or molecularly dispersed in MO. All three thermograms of blank LCNPs (Figure 4A[a]), AE-LCNPs (Figure 4A[b]), and AE-PEGylated LCNPs (Figure 4A[c]) exhibited the reported characteristic peak of mannitol used to facilitate lyophilization step of LCNPs at 163°C.35


Stealth, biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells: in vitro and in vivo studies
(A) DSC thermograms of (a) blank LCNPs, (b) AE-LCNPs (F6), (c) AE-PEGylated LCNPs (F13), and (d) free AE. (B) IR spectra of blank LCNPs, AE-LCNPs (F6), AE-PEGylated LCNPs (F13), and free AE. (C) XRD patterns of free AE (A), blank LCNPs (B), AE-LCNPs (C) (F6), and AE-PEGylated LCNPs (D) (F13). (D) In vitro release study of free AE, AE-LCNPs (F6), and AE-PEGylated LCNPs (F13) in phosphate buffer, pH 7.4; 1% Tween 80 at 75 rpm and 37°C using dialysis bag method.Abbreviations: AE, aloe-emodin; DSC, differential scanning calorimetry; IR, infrared; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; XRD, X-ray powder diffraction.
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Related In: Results  -  Collection

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f4-ijn-11-4799: (A) DSC thermograms of (a) blank LCNPs, (b) AE-LCNPs (F6), (c) AE-PEGylated LCNPs (F13), and (d) free AE. (B) IR spectra of blank LCNPs, AE-LCNPs (F6), AE-PEGylated LCNPs (F13), and free AE. (C) XRD patterns of free AE (A), blank LCNPs (B), AE-LCNPs (C) (F6), and AE-PEGylated LCNPs (D) (F13). (D) In vitro release study of free AE, AE-LCNPs (F6), and AE-PEGylated LCNPs (F13) in phosphate buffer, pH 7.4; 1% Tween 80 at 75 rpm and 37°C using dialysis bag method.Abbreviations: AE, aloe-emodin; DSC, differential scanning calorimetry; IR, infrared; LCNPs, liquid crystalline nanoparticles; PEG, polyethylene glycol; XRD, X-ray powder diffraction.
Mentions: DSC is a common and reliable method used to investigate any change that could be occurred in drug crystallinity during nanoparticle formulation (Figure 4A). The thermogram of AE showed one sharp endothermal peak at 223°C (Figure 4A[d]). DSC of AE-LCNPs (Figure 4A[b]) and AE-PEGylated LCNPs (Figure 4A[c]) showed that the characteristic endothermal peak of the drug disappeared indicating that the encapsulated AE in LCNPs was converted to its amorphous state or molecularly dispersed in MO. All three thermograms of blank LCNPs (Figure 4A[a]), AE-LCNPs (Figure 4A[b]), and AE-PEGylated LCNPs (Figure 4A[c]) exhibited the reported characteristic peak of mannitol used to facilitate lyophilization step of LCNPs at 163°C.35

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.