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In Vitro and In Vivo Evaluations of PLGA Microspheres Containing Nalmefene.

Xie X, Lin W, Xing C, Yang Y, Chi Q, Zhang H, Li Y, Li Z, Yang Y, Yang Z, Li M - PLoS ONE (2015)

Bottom Line: Pharmacokinetics study indicated that the prepared microspheres could provide a relatively constant of nalmefene plasma concentration for at least one month in rats.Pharmacodynamics studies revealed that the drug loaded microspheres could produce a long-acting antagonism efficacy on rats.These results demonstrated the promising application of injectable PLGA microspheres containing nalmefene for the long-term treatment of alcohol dependence.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, PR China.

ABSTRACT
Poor patient compliance, untoward reactions and unstable blood drug levels after the bolus administration are impeding the pharmacotherapy for insobriety. A long-acting preparation may address these limitations. The aim of this paper was to further investigate the in vitro characteristics and in vivo performances of nalmefene microspheres. Nalmefene was blended with poly (lactide-co-glycolide) (PLGA) to prepare the target microspheres by an O/O emulsification solvent evaporation method. The prepared microspheres exhibited a controlled release profile of nalmefene in vitro over 4 weeks, which was well fitted with a first-order model. In vitro degradation study showed that the drug release in vitro was dominated by both drug diffusion and polymer degradation mechanisms. Pharmacokinetics study indicated that the prepared microspheres could provide a relatively constant of nalmefene plasma concentration for at least one month in rats. The in vivo pharmacokinetics profile was well correlated with the in vitro drug release. Pharmacodynamics studies revealed that the drug loaded microspheres could produce a long-acting antagonism efficacy on rats. These results demonstrated the promising application of injectable PLGA microspheres containing nalmefene for the long-term treatment of alcohol dependence.

No MeSH data available.


Related in: MedlinePlus

Mean plasma drug concentration-time curve of nalmefene in rats following the single subcutaneous injection of drug loaded microspheres (n = 6).
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pone.0125953.g007: Mean plasma drug concentration-time curve of nalmefene in rats following the single subcutaneous injection of drug loaded microspheres (n = 6).

Mentions: The mean plasma drug concentration versus time curves for nalmefene were shown in Figs 6 and 7, corresponding to the subcutaneous administration of nalmefene solution (3 mg/kg) and nalmefene encapsulated microspheres (90 mg/kg), respectively. As displayed in Fig 6, after the single injection of nalmefene solution, the plasma drug concentration quickly reached its maximum value (689.16 ± 181.26 ng/mL) in 2 min, and then it declined fast, left around 10% of the Cmax value 2 h later, which implied a rapid in vivo elimination of nalmefene exist in rats.


In Vitro and In Vivo Evaluations of PLGA Microspheres Containing Nalmefene.

Xie X, Lin W, Xing C, Yang Y, Chi Q, Zhang H, Li Y, Li Z, Yang Y, Yang Z, Li M - PLoS ONE (2015)

Mean plasma drug concentration-time curve of nalmefene in rats following the single subcutaneous injection of drug loaded microspheres (n = 6).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4418713&req=5

pone.0125953.g007: Mean plasma drug concentration-time curve of nalmefene in rats following the single subcutaneous injection of drug loaded microspheres (n = 6).
Mentions: The mean plasma drug concentration versus time curves for nalmefene were shown in Figs 6 and 7, corresponding to the subcutaneous administration of nalmefene solution (3 mg/kg) and nalmefene encapsulated microspheres (90 mg/kg), respectively. As displayed in Fig 6, after the single injection of nalmefene solution, the plasma drug concentration quickly reached its maximum value (689.16 ± 181.26 ng/mL) in 2 min, and then it declined fast, left around 10% of the Cmax value 2 h later, which implied a rapid in vivo elimination of nalmefene exist in rats.

Bottom Line: Pharmacokinetics study indicated that the prepared microspheres could provide a relatively constant of nalmefene plasma concentration for at least one month in rats.Pharmacodynamics studies revealed that the drug loaded microspheres could produce a long-acting antagonism efficacy on rats.These results demonstrated the promising application of injectable PLGA microspheres containing nalmefene for the long-term treatment of alcohol dependence.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, PR China.

ABSTRACT
Poor patient compliance, untoward reactions and unstable blood drug levels after the bolus administration are impeding the pharmacotherapy for insobriety. A long-acting preparation may address these limitations. The aim of this paper was to further investigate the in vitro characteristics and in vivo performances of nalmefene microspheres. Nalmefene was blended with poly (lactide-co-glycolide) (PLGA) to prepare the target microspheres by an O/O emulsification solvent evaporation method. The prepared microspheres exhibited a controlled release profile of nalmefene in vitro over 4 weeks, which was well fitted with a first-order model. In vitro degradation study showed that the drug release in vitro was dominated by both drug diffusion and polymer degradation mechanisms. Pharmacokinetics study indicated that the prepared microspheres could provide a relatively constant of nalmefene plasma concentration for at least one month in rats. The in vivo pharmacokinetics profile was well correlated with the in vitro drug release. Pharmacodynamics studies revealed that the drug loaded microspheres could produce a long-acting antagonism efficacy on rats. These results demonstrated the promising application of injectable PLGA microspheres containing nalmefene for the long-term treatment of alcohol dependence.

No MeSH data available.


Related in: MedlinePlus