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Pharmacokinetics and enhanced oral bioavailability in beagle dogs of cyclosporine A encapsulated in glyceryl monooleate/poloxamer 407 cubic nanoparticles.

Lai J, Lu Y, Yin Z, Hu F, Wu W - Int J Nanomedicine (2010)

Bottom Line: The results of a pharmacokinetic study in beagle dogs showed improved absorption of CyA from cubic nanoparticles as compared to microemulsion-based Neoral((R)); higher C(max) (1371.18 +/- 37.34 vs 969.68 +/- 176.3 ng mL(-1)), higher AUC(0-t) (7757.21 +/- 1093.64 vs 4739.52 +/- 806.30 ng h mL(-1)) and AUC(0-infinity) (9004.77 +/- 1090.38 vs 5462.31 +/- 930.76 ng h mL(-1)).The relative oral bioavailability of CyA cubic nanoparticles calculated on the basis of AUC(0-infinity) was about 178% as compared to Neoral((R)).The enhanced bioavailability of CyA is likely due to facilitated absorption by cubic nanoparticles rather than improved release.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, China.

ABSTRACT
Efforts to improve the oral bioavailability of cyclosporine A (CyA) remains a challenge in the field of drug delivery. In this study, glyceryl monooleate (GMO)/poloxamer 407 cubic nanoparticles were evaluated as potential vehicles to improve the oral bioavailability of CyA. Cubic nanoparticles were prepared via the fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by sonication and homogenization. The cubic inner structure formed was verified using Cryo-TEM. The mean diameters of the nanoparticles were about 180 nm, and the entrapment efficiency of these particles for CyA was over 85%. The in vitro release of CyA from these nanoparticles was less than 5% at 12 h. The results of a pharmacokinetic study in beagle dogs showed improved absorption of CyA from cubic nanoparticles as compared to microemulsion-based Neoral((R)); higher C(max) (1371.18 +/- 37.34 vs 969.68 +/- 176.3 ng mL(-1)), higher AUC(0-t) (7757.21 +/- 1093.64 vs 4739.52 +/- 806.30 ng h mL(-1)) and AUC(0-infinity) (9004.77 +/- 1090.38 vs 5462.31 +/- 930.76 ng h mL(-1)). The relative oral bioavailability of CyA cubic nanoparticles calculated on the basis of AUC(0-infinity) was about 178% as compared to Neoral((R)). The enhanced bioavailability of CyA is likely due to facilitated absorption by cubic nanoparticles rather than improved release.

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Size distribution of CyA-loaded cubic nanoparticles after sonication A) and homogenization at 689 bar for five cycles B).
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f2-ijn-5-013: Size distribution of CyA-loaded cubic nanoparticles after sonication A) and homogenization at 689 bar for five cycles B).

Mentions: During the sonication procedure, the cubic phase gel was efficiently disrupted. Particle size analysis gave a mean diameter of 200–300 nm and a wide particle size distribution ranging from 30 nm to 1000 nm (Figure 2A). After homogenization, the mean diameter of the particles was reduced to about 180 nm with a narrower lognormal size distribution within 70–300 nm (Figure 2B). The GMO/poloxamer 407 ratio had no significant effect (P < 0.05) on the particle size except at the ratio of 100/20 (Figure 3A). Increasing the homogenization pressure to 670 bar could efficiently reduce the particle size (Figure 3B) as a result of increased energy input, whereas the homogenization cycles, either three or five, appeared to have no significant effect on particle size except at 350 bar (Figure 3B). It seems that homogenization was more efficient at higher pressure and three homogenization cycles were enough to obtain stable particle size, while at lower pressures more homogenization cycles were needed to obtain cubic nanoparticles of smaller diameters. Under the homogenization conditions in this study, cubic nanoparticles with reproducible particle size and distribution could be obtained.


Pharmacokinetics and enhanced oral bioavailability in beagle dogs of cyclosporine A encapsulated in glyceryl monooleate/poloxamer 407 cubic nanoparticles.

Lai J, Lu Y, Yin Z, Hu F, Wu W - Int J Nanomedicine (2010)

Size distribution of CyA-loaded cubic nanoparticles after sonication A) and homogenization at 689 bar for five cycles B).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2819904&req=5

f2-ijn-5-013: Size distribution of CyA-loaded cubic nanoparticles after sonication A) and homogenization at 689 bar for five cycles B).
Mentions: During the sonication procedure, the cubic phase gel was efficiently disrupted. Particle size analysis gave a mean diameter of 200–300 nm and a wide particle size distribution ranging from 30 nm to 1000 nm (Figure 2A). After homogenization, the mean diameter of the particles was reduced to about 180 nm with a narrower lognormal size distribution within 70–300 nm (Figure 2B). The GMO/poloxamer 407 ratio had no significant effect (P < 0.05) on the particle size except at the ratio of 100/20 (Figure 3A). Increasing the homogenization pressure to 670 bar could efficiently reduce the particle size (Figure 3B) as a result of increased energy input, whereas the homogenization cycles, either three or five, appeared to have no significant effect on particle size except at 350 bar (Figure 3B). It seems that homogenization was more efficient at higher pressure and three homogenization cycles were enough to obtain stable particle size, while at lower pressures more homogenization cycles were needed to obtain cubic nanoparticles of smaller diameters. Under the homogenization conditions in this study, cubic nanoparticles with reproducible particle size and distribution could be obtained.

Bottom Line: The results of a pharmacokinetic study in beagle dogs showed improved absorption of CyA from cubic nanoparticles as compared to microemulsion-based Neoral((R)); higher C(max) (1371.18 +/- 37.34 vs 969.68 +/- 176.3 ng mL(-1)), higher AUC(0-t) (7757.21 +/- 1093.64 vs 4739.52 +/- 806.30 ng h mL(-1)) and AUC(0-infinity) (9004.77 +/- 1090.38 vs 5462.31 +/- 930.76 ng h mL(-1)).The relative oral bioavailability of CyA cubic nanoparticles calculated on the basis of AUC(0-infinity) was about 178% as compared to Neoral((R)).The enhanced bioavailability of CyA is likely due to facilitated absorption by cubic nanoparticles rather than improved release.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, China.

ABSTRACT
Efforts to improve the oral bioavailability of cyclosporine A (CyA) remains a challenge in the field of drug delivery. In this study, glyceryl monooleate (GMO)/poloxamer 407 cubic nanoparticles were evaluated as potential vehicles to improve the oral bioavailability of CyA. Cubic nanoparticles were prepared via the fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by sonication and homogenization. The cubic inner structure formed was verified using Cryo-TEM. The mean diameters of the nanoparticles were about 180 nm, and the entrapment efficiency of these particles for CyA was over 85%. The in vitro release of CyA from these nanoparticles was less than 5% at 12 h. The results of a pharmacokinetic study in beagle dogs showed improved absorption of CyA from cubic nanoparticles as compared to microemulsion-based Neoral((R)); higher C(max) (1371.18 +/- 37.34 vs 969.68 +/- 176.3 ng mL(-1)), higher AUC(0-t) (7757.21 +/- 1093.64 vs 4739.52 +/- 806.30 ng h mL(-1)) and AUC(0-infinity) (9004.77 +/- 1090.38 vs 5462.31 +/- 930.76 ng h mL(-1)). The relative oral bioavailability of CyA cubic nanoparticles calculated on the basis of AUC(0-infinity) was about 178% as compared to Neoral((R)). The enhanced bioavailability of CyA is likely due to facilitated absorption by cubic nanoparticles rather than improved release.

Show MeSH
Related in: MedlinePlus