Limits...
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.

Show MeSH

Related in: MedlinePlus

Pseudoternary phase diagrams of nanoemulsions composed of IPM or LT as mixed surfactants, PEG400 or propylene glycol as cosurfactants, and water.Notes: (A–C) LT/PEG400 at the weight ratios of 1:1, 2:1, and 1:2, respectively. (D–F) LT/propylene glycol at the weight ratios of 1:1, 2:1, and 1:2, respectively. The dark outline represents the area of nanoemulsion produced by the surfactant/cosurfactant combination.Abbreviations: IPM, isopropyl myristate; LT, soy-lecithin/tween-80 with the weight ratio of 1:2; PEG400, polyethylene glycol 400.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3794992&req=5

f3-ijn-8-3769: Pseudoternary phase diagrams of nanoemulsions composed of IPM or LT as mixed surfactants, PEG400 or propylene glycol as cosurfactants, and water.Notes: (A–C) LT/PEG400 at the weight ratios of 1:1, 2:1, and 1:2, respectively. (D–F) LT/propylene glycol at the weight ratios of 1:1, 2:1, and 1:2, respectively. The dark outline represents the area of nanoemulsion produced by the surfactant/cosurfactant combination.Abbreviations: IPM, isopropyl myristate; LT, soy-lecithin/tween-80 with the weight ratio of 1:2; PEG400, polyethylene glycol 400.

Mentions: Because phospholipids act as natural emulsifiers, soy-lecithin is generally considered to be safe for humans. Additionally, nonionic surfactants are less toxic than ionic surfactants.34 The combination of soy-lecithin and tween-80 as mixed surfactants was investigated in the preliminary experiment. The results showed that the highest emulsification efficiency was obtained in the case of LT (soy-lecithin and tween-80 with the weight ratio of 1:2 as mixed surfactants). Therefore, on the basis of results of solubility studies and preliminary experiments, we primarily chose nanoemulsion formulations composed of IPM, LT, and water in the presence of cosurfactant (PEG400 or propylene glycol). To determine the appropriate concentration range of components for the formation of nanoemulsion regions, we constructed pseudoternary phase diagrams with various weight ratios of LT/PEG400 or LT/propylene glycol (Figure 3). Figure 3 illustrates that the areas of nanoemulsion produced by various ratios (1:1, 2:1, 1:2) of LT/PEG400 or LT/propylene glycol were different. The area formed by LT/PEG400 was larger than that of LT/propylene glycol, indicating that the formation of nanoemul-sions was affected by the cosurfactant types. Furthermore, the largest area of nanoemulsion regions was observed in the case of LT/PEG400 (2:1).


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)

Pseudoternary phase diagrams of nanoemulsions composed of IPM or LT as mixed surfactants, PEG400 or propylene glycol as cosurfactants, and water.Notes: (A–C) LT/PEG400 at the weight ratios of 1:1, 2:1, and 1:2, respectively. (D–F) LT/propylene glycol at the weight ratios of 1:1, 2:1, and 1:2, respectively. The dark outline represents the area of nanoemulsion produced by the surfactant/cosurfactant combination.Abbreviations: IPM, isopropyl myristate; LT, soy-lecithin/tween-80 with the weight ratio of 1:2; PEG400, polyethylene glycol 400.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ijn-8-3769: Pseudoternary phase diagrams of nanoemulsions composed of IPM or LT as mixed surfactants, PEG400 or propylene glycol as cosurfactants, and water.Notes: (A–C) LT/PEG400 at the weight ratios of 1:1, 2:1, and 1:2, respectively. (D–F) LT/propylene glycol at the weight ratios of 1:1, 2:1, and 1:2, respectively. The dark outline represents the area of nanoemulsion produced by the surfactant/cosurfactant combination.Abbreviations: IPM, isopropyl myristate; LT, soy-lecithin/tween-80 with the weight ratio of 1:2; PEG400, polyethylene glycol 400.
Mentions: Because phospholipids act as natural emulsifiers, soy-lecithin is generally considered to be safe for humans. Additionally, nonionic surfactants are less toxic than ionic surfactants.34 The combination of soy-lecithin and tween-80 as mixed surfactants was investigated in the preliminary experiment. The results showed that the highest emulsification efficiency was obtained in the case of LT (soy-lecithin and tween-80 with the weight ratio of 1:2 as mixed surfactants). Therefore, on the basis of results of solubility studies and preliminary experiments, we primarily chose nanoemulsion formulations composed of IPM, LT, and water in the presence of cosurfactant (PEG400 or propylene glycol). To determine the appropriate concentration range of components for the formation of nanoemulsion regions, we constructed pseudoternary phase diagrams with various weight ratios of LT/PEG400 or LT/propylene glycol (Figure 3). Figure 3 illustrates that the areas of nanoemulsion produced by various ratios (1:1, 2:1, 1:2) of LT/PEG400 or LT/propylene glycol were different. The area formed by LT/PEG400 was larger than that of LT/propylene glycol, indicating that the formation of nanoemul-sions was affected by the cosurfactant types. Furthermore, the largest area of nanoemulsion regions was observed in the case of LT/PEG400 (2:1).

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