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Nanoemulsion improves the oral bioavailability of baicalin in rats: in vitro and in vivo evaluation.

Zhao L, Wei Y, Huang Y, He B, Zhou Y, Fu J - Int J Nanomedicine (2013)

Bottom Line: After dilution 30-fold with water, the solubilization capacity of BAN-1 and BAN-2 did not change.In vitro release results showed sustained-release characteristics.In conclusion, these results demonstrated that the baicalin-loaded nanoemulsion formulation, in particular BAN-1, was very effective for improving the oral bioavailability of baicalin and exhibited great potential for future clinical application.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Luzhou Medical College, Luzhou City, Sichuan Province, People's Republic of China ; Drug and Functional Food Research Center, Luzhou Medical College, Luzhou City, Sichuan Province, People's Republic of China.

ABSTRACT
Baicalin is one of the main bioactive flavone glucuronides derived as a medicinal herb from the dried roots of Scutellaria baicalensis Georgi, and it is widely used for the treatment of fever, inflammation, and other conditions. Due to baicalin's poor solubility in water, its absolute bioavailability after oral administration is only 2.2%. The objective of this study was to develop a novel baicalin-loaded nanoemulsion to improve the oral bioavailability of baicalin. Based on the result of pseudoternary phase diagram, the nanoemulsion formulation consisting of soy-lecithin, tween-80, polyethylene glycol 400, isopropyl myristate, and water (1:2:1.5:3.75:8.25, w/w) was selected for further study. Baicalin-loaded nanoemulsions (BAN-1 and BAN-2) were prepared by internal or external drug addition and in vivo and in vitro evaluations were performed. The results showed that the mean droplet size, polydispersity index, and drug content of BAN-1 and BAN-2 were 91.2 ± 2.36 nm and 89.7 ± 3.05 nm, 0.313 ± 0.002 and 0.265 ± 0.001, and 98.56% ± 0.79% and 99.40% ± 0.51%, respectively. Transmission electron microscopy revealed spherical globules and confirmed droplet size analysis. After dilution 30-fold with water, the solubilization capacity of BAN-1 and BAN-2 did not change. In vitro release results showed sustained-release characteristics. BAN-1 formulation was stable for at least 6 months and was more stable than BAN-2. In rats, the area under the plasma drug concentration-time curve value of BAN-1 was 1.8-fold and 7-fold greater than those of BAN-2 and free baicalin suspension after oral administration at a dose of 100 mg/kg. In conclusion, these results demonstrated that the baicalin-loaded nanoemulsion formulation, in particular BAN-1, was very effective for improving the oral bioavailability of baicalin and exhibited great potential for future clinical application.

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Plasma concentration-time profiles of baicalin-loaded nanoemulsions in rats after oral administration of BAN-1, BAN-2, and BA control.Note: Data are expressed as mean ± standard deviation (n = 3).Abbreviations: BAN-1, baicalin-loaded nanoemulsion created by dissolution of baicalin in PEG400 and mixing with soy-lecithin, tween-80, IPM, and water; BAN-2, baicalin-loaded nanoemulsion created by dissolution of baicalin in the final nanoemulsion formulations; BA control, free baicalin suspension (baicalin suspended in 0.5% sodium carboxymethyl cellulose solution).
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f8-ijn-8-3769: Plasma concentration-time profiles of baicalin-loaded nanoemulsions in rats after oral administration of BAN-1, BAN-2, and BA control.Note: Data are expressed as mean ± standard deviation (n = 3).Abbreviations: BAN-1, baicalin-loaded nanoemulsion created by dissolution of baicalin in PEG400 and mixing with soy-lecithin, tween-80, IPM, and water; BAN-2, baicalin-loaded nanoemulsion created by dissolution of baicalin in the final nanoemulsion formulations; BA control, free baicalin suspension (baicalin suspended in 0.5% sodium carboxymethyl cellulose solution).

Mentions: The plasma drug concentration-time curve is shown in Figure 8, and the main pharmacokinetic parameters are summarized in Table 3. A significant difference between the pharmacokinetic behavior of baicalin-loaded nanoemulsion and free baicalin suspension was observed (Figure 8). At each time point, the plasma drug concentration of BAN-1 and BAN-2 was much higher than that of free baicalin suspension. The peak concentration (Cmax) of baicalin from BAN-1 and BAN-2 was 3.155 ± 0.132 mg/L and 4.625 ± 0.203 mg/L, respectively, which was about 3–4 times that of free baicalin suspension (1.143 ± 0.105 mg/L) – a significant increase (P < 0.05). The AUC(0–∞) value of baicalin in rats treated with BAN-1 or BAN-2 was 98.439 ± 4.579 mg/L*h and 54.443 ± 3.879 mg/L*h, respectively, which was improved more than 7 and 4 times than that of free baicalin suspension (13.681 ± 1.092 mg/L*h) (P < 0.05). In addition, the MRT and t1/2 value of BAN-1 was about 3.5-fold greater than that of BAN-2 and the reference preparation. It was reported that the oral bioavailability of baicalin was enhanced approximately 2.6 times by solid lipid nanoparticles.38 However, in the present study, unexpected results demonstrated that the baicalin-loaded nanoemulsion BAN-1 was much more effective than nanoparticle, which could be attributed to enhanced permeability induced by surfactant and cosurfactant, uptake of BAN-1 in gastrointestinal tract, and the sustained-release of drug from BAN-1. In this study, the AUC(0–∞) value of BAN-1 was 1.8-fold higher that of BAN-2, which could have resulted from the longer MRT(0–∞) and t1/2 values, in combination with being more stable.


Nanoemulsion improves the oral bioavailability of baicalin in rats: in vitro and in vivo evaluation.

Zhao L, Wei Y, Huang Y, He B, Zhou Y, Fu J - Int J Nanomedicine (2013)

Plasma concentration-time profiles of baicalin-loaded nanoemulsions in rats after oral administration of BAN-1, BAN-2, and BA control.Note: Data are expressed as mean ± standard deviation (n = 3).Abbreviations: BAN-1, baicalin-loaded nanoemulsion created by dissolution of baicalin in PEG400 and mixing with soy-lecithin, tween-80, IPM, and water; BAN-2, baicalin-loaded nanoemulsion created by dissolution of baicalin in the final nanoemulsion formulations; BA control, free baicalin suspension (baicalin suspended in 0.5% sodium carboxymethyl cellulose solution).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3794992&req=5

f8-ijn-8-3769: Plasma concentration-time profiles of baicalin-loaded nanoemulsions in rats after oral administration of BAN-1, BAN-2, and BA control.Note: Data are expressed as mean ± standard deviation (n = 3).Abbreviations: BAN-1, baicalin-loaded nanoemulsion created by dissolution of baicalin in PEG400 and mixing with soy-lecithin, tween-80, IPM, and water; BAN-2, baicalin-loaded nanoemulsion created by dissolution of baicalin in the final nanoemulsion formulations; BA control, free baicalin suspension (baicalin suspended in 0.5% sodium carboxymethyl cellulose solution).
Mentions: The plasma drug concentration-time curve is shown in Figure 8, and the main pharmacokinetic parameters are summarized in Table 3. A significant difference between the pharmacokinetic behavior of baicalin-loaded nanoemulsion and free baicalin suspension was observed (Figure 8). At each time point, the plasma drug concentration of BAN-1 and BAN-2 was much higher than that of free baicalin suspension. The peak concentration (Cmax) of baicalin from BAN-1 and BAN-2 was 3.155 ± 0.132 mg/L and 4.625 ± 0.203 mg/L, respectively, which was about 3–4 times that of free baicalin suspension (1.143 ± 0.105 mg/L) – a significant increase (P < 0.05). The AUC(0–∞) value of baicalin in rats treated with BAN-1 or BAN-2 was 98.439 ± 4.579 mg/L*h and 54.443 ± 3.879 mg/L*h, respectively, which was improved more than 7 and 4 times than that of free baicalin suspension (13.681 ± 1.092 mg/L*h) (P < 0.05). In addition, the MRT and t1/2 value of BAN-1 was about 3.5-fold greater than that of BAN-2 and the reference preparation. It was reported that the oral bioavailability of baicalin was enhanced approximately 2.6 times by solid lipid nanoparticles.38 However, in the present study, unexpected results demonstrated that the baicalin-loaded nanoemulsion BAN-1 was much more effective than nanoparticle, which could be attributed to enhanced permeability induced by surfactant and cosurfactant, uptake of BAN-1 in gastrointestinal tract, and the sustained-release of drug from BAN-1. In this study, the AUC(0–∞) value of BAN-1 was 1.8-fold higher that of BAN-2, which could have resulted from the longer MRT(0–∞) and t1/2 values, in combination with being more stable.

Bottom Line: After dilution 30-fold with water, the solubilization capacity of BAN-1 and BAN-2 did not change.In vitro release results showed sustained-release characteristics.In conclusion, these results demonstrated that the baicalin-loaded nanoemulsion formulation, in particular BAN-1, was very effective for improving the oral bioavailability of baicalin and exhibited great potential for future clinical application.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Luzhou Medical College, Luzhou City, Sichuan Province, People's Republic of China ; Drug and Functional Food Research Center, Luzhou Medical College, Luzhou City, Sichuan Province, People's Republic of China.

ABSTRACT
Baicalin is one of the main bioactive flavone glucuronides derived as a medicinal herb from the dried roots of Scutellaria baicalensis Georgi, and it is widely used for the treatment of fever, inflammation, and other conditions. Due to baicalin's poor solubility in water, its absolute bioavailability after oral administration is only 2.2%. The objective of this study was to develop a novel baicalin-loaded nanoemulsion to improve the oral bioavailability of baicalin. Based on the result of pseudoternary phase diagram, the nanoemulsion formulation consisting of soy-lecithin, tween-80, polyethylene glycol 400, isopropyl myristate, and water (1:2:1.5:3.75:8.25, w/w) was selected for further study. Baicalin-loaded nanoemulsions (BAN-1 and BAN-2) were prepared by internal or external drug addition and in vivo and in vitro evaluations were performed. The results showed that the mean droplet size, polydispersity index, and drug content of BAN-1 and BAN-2 were 91.2 ± 2.36 nm and 89.7 ± 3.05 nm, 0.313 ± 0.002 and 0.265 ± 0.001, and 98.56% ± 0.79% and 99.40% ± 0.51%, respectively. Transmission electron microscopy revealed spherical globules and confirmed droplet size analysis. After dilution 30-fold with water, the solubilization capacity of BAN-1 and BAN-2 did not change. In vitro release results showed sustained-release characteristics. BAN-1 formulation was stable for at least 6 months and was more stable than BAN-2. In rats, the area under the plasma drug concentration-time curve value of BAN-1 was 1.8-fold and 7-fold greater than those of BAN-2 and free baicalin suspension after oral administration at a dose of 100 mg/kg. In conclusion, these results demonstrated that the baicalin-loaded nanoemulsion formulation, in particular BAN-1, was very effective for improving the oral bioavailability of baicalin and exhibited great potential for future clinical application.

Show MeSH
Related in: MedlinePlus