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Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits.

Zhang L, Li Y, Zhang C, Wang Y, Song C - Int J Nanomedicine (2009)

Bottom Line: The DEX-NPs maintained a sustained release of DEX for about 50 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.85 mg/L(-1).Based on the areas under the curve, the bioavailability of DEX in the experimental group was significantly higher than that in the control group injected with regular DEX.These results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin 300192, China.

ABSTRACT
The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX)-loaded poly(lactic acid-co-glycolic acid) nanoparticles (DEX-NPs) in rabbits after intravitreal injection. The DEX-NPs were prepared and characterized in terms of morphology, particle size and size distribution, encapsulation efficiency, and in vitro release. Ophthalmic investigations were performed, including fundus observation and photography, intraocular pressure measurement, and B-scan ocular ultrasonography. There were no abnormalities up to 50 days after administration of DEX-NPs in rabbits. The DEX concentrations in plasma and the ocular tissues such as the cornea, aqueous humor, lens, iris, vitreous humor, and chorioretina were determined by high-pressure liquid chromatography. The DEX-NPs maintained a sustained release of DEX for about 50 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.85 mg/L(-1). Based on the areas under the curve, the bioavailability of DEX in the experimental group was significantly higher than that in the control group injected with regular DEX. These results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.

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Related in: MedlinePlus

DEX concentrations in vitreous after intravitreal injection in rabbits of (▪) DEX and (○) DEX-NPs (mean ± SD, n = 3).Abbreviations: DEX, dexamethasone; DEX-NPs, dexamethasone-loaded PLGA nanoparticles; PLGA, Poly(lactic acid–co-glycolic acid); SD, standard deviation.
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f4-ijn-4-175: DEX concentrations in vitreous after intravitreal injection in rabbits of (▪) DEX and (○) DEX-NPs (mean ± SD, n = 3).Abbreviations: DEX, dexamethasone; DEX-NPs, dexamethasone-loaded PLGA nanoparticles; PLGA, Poly(lactic acid–co-glycolic acid); SD, standard deviation.

Mentions: The DEX concentration of all the samples was determined by HPLC at each time point (Tables 1 and 2). The DEX concentration in cornea, aqueous humor, and lens were all below the detectable limit (10 μg/L−1) of the HPLC assay, and could only be detected in the iris on the first day after injection, with a low value of 0.08 ± 0.02 g/g−1. The DEX-loaded nanoparticles maintained a sustained release of DEX for at least 50 days in the vitreous with a maximum concentration (Cmax) of 8.48 ± 1.19 mg/L−1, and provided relatively constant DEX levels for more than 30 days. In contrast, in the control group treated with DEX, the Cmax in the vitreous was 10.73 ± 5.43 mg/L−1, with only trace amounts of DEX being detected on the 7th day after injection, and the DEX concentration dropping below the detectable limit (10 μg/L−1) before the 14th day after injection (Figure 4). The vitreous DEX concentration in the experimental animals treated with DEX-NPs was higher than that of the plasma, with mean vitreous DEX concentration of 3.85 mg/L−1, which was significantly higher (P < 0.001) than that of the plasma (0.7 mg/L−1) (Figure 5). Comparing the experimental group and the control group, the drug concentrations in the vitreous (P = 0.86), chorioretina (P = 0.74), and plasma (P = 0.156) showed no significant differences.


Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits.

Zhang L, Li Y, Zhang C, Wang Y, Song C - Int J Nanomedicine (2009)

DEX concentrations in vitreous after intravitreal injection in rabbits of (▪) DEX and (○) DEX-NPs (mean ± SD, n = 3).Abbreviations: DEX, dexamethasone; DEX-NPs, dexamethasone-loaded PLGA nanoparticles; PLGA, Poly(lactic acid–co-glycolic acid); SD, standard deviation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747352&req=5

f4-ijn-4-175: DEX concentrations in vitreous after intravitreal injection in rabbits of (▪) DEX and (○) DEX-NPs (mean ± SD, n = 3).Abbreviations: DEX, dexamethasone; DEX-NPs, dexamethasone-loaded PLGA nanoparticles; PLGA, Poly(lactic acid–co-glycolic acid); SD, standard deviation.
Mentions: The DEX concentration of all the samples was determined by HPLC at each time point (Tables 1 and 2). The DEX concentration in cornea, aqueous humor, and lens were all below the detectable limit (10 μg/L−1) of the HPLC assay, and could only be detected in the iris on the first day after injection, with a low value of 0.08 ± 0.02 g/g−1. The DEX-loaded nanoparticles maintained a sustained release of DEX for at least 50 days in the vitreous with a maximum concentration (Cmax) of 8.48 ± 1.19 mg/L−1, and provided relatively constant DEX levels for more than 30 days. In contrast, in the control group treated with DEX, the Cmax in the vitreous was 10.73 ± 5.43 mg/L−1, with only trace amounts of DEX being detected on the 7th day after injection, and the DEX concentration dropping below the detectable limit (10 μg/L−1) before the 14th day after injection (Figure 4). The vitreous DEX concentration in the experimental animals treated with DEX-NPs was higher than that of the plasma, with mean vitreous DEX concentration of 3.85 mg/L−1, which was significantly higher (P < 0.001) than that of the plasma (0.7 mg/L−1) (Figure 5). Comparing the experimental group and the control group, the drug concentrations in the vitreous (P = 0.86), chorioretina (P = 0.74), and plasma (P = 0.156) showed no significant differences.

Bottom Line: The DEX-NPs maintained a sustained release of DEX for about 50 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.85 mg/L(-1).Based on the areas under the curve, the bioavailability of DEX in the experimental group was significantly higher than that in the control group injected with regular DEX.These results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin 300192, China.

ABSTRACT
The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX)-loaded poly(lactic acid-co-glycolic acid) nanoparticles (DEX-NPs) in rabbits after intravitreal injection. The DEX-NPs were prepared and characterized in terms of morphology, particle size and size distribution, encapsulation efficiency, and in vitro release. Ophthalmic investigations were performed, including fundus observation and photography, intraocular pressure measurement, and B-scan ocular ultrasonography. There were no abnormalities up to 50 days after administration of DEX-NPs in rabbits. The DEX concentrations in plasma and the ocular tissues such as the cornea, aqueous humor, lens, iris, vitreous humor, and chorioretina were determined by high-pressure liquid chromatography. The DEX-NPs maintained a sustained release of DEX for about 50 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.85 mg/L(-1). Based on the areas under the curve, the bioavailability of DEX in the experimental group was significantly higher than that in the control group injected with regular DEX. These results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.

Show MeSH
Related in: MedlinePlus