Pharmacokinetics and brain distribution studies of perphenazine-loaded solid lipid nanoparticles

Abstract

Background

Perphenazine (PPZ) is a typical antipsychotic that is mainly administrated for the treatment of schizophrenia. Due to its highly lipophilic nature and extensive hepatic first-pass metabolism, its oral bioavailability is low (40%).

Objective

The novel nanocarriers like solid lipid nanoparticles (SLN) have been reported to be highly effective for improving the therapeutic effect of drugs. Therefore the main scope of the present investigation was the evaluation of in vivo characteristics of PPZ-SLN in terms of pharmacokinetic parameters and brain distribution.

Methods

The PPZ-SLN was prepared by the solvent-emulsification and evaporation method. The storage stability of PPZ-SLN and empty SLN powders was studied for 3 months. In vivo pharmacokinetic studies and brain distribution evaluations were performed following a single oral dose administration of PPZ and PPZ-SLN suspensions on male Wistar rats. An HPLC method was established and validated for the quantitative determination of PPZ in plasma and brain samples.

Results

The storage stability studies revealed the good storage stability of the both PPZ-SLN and empty SLN at 4 °C. Compared to PPZ suspension, the relative bioavailability and the brain distribution of PPZ-SLN were increased up to 2-fold and 16-fold, respectively. Mean residence time (MRT) and half-life (t_1/2) of PPZ-SLN were significantly (p value < 0.01) increased in both plasma and brain homogenate compared to PPZ suspension.

Conclusion

The significant improvement in the pharmacokinetic properties of PPZ following one oral dose indicates that SLN is a promising drug delivery system for PPZ and shows a high potential for successful brain delivery of this antipsychotic.

Keywords:

• Perphenazine
• solid lipid nanoparticles
• brain targeting
• blood–brain barrier
• oral drug delivery

Acknowledgments

The authors thank Masoumeh Kurd (PhD.) and Nafiseh Faraji (M.Sc.) for their skillful technical and practical assistance. The Laboratory of Animal Center of Hamadan University of Medical Sciences is acknowledged for providing a pleasant working atmosphere and excellent care for the animals.

Disclosure statement

The authors declare that they have no conflicts of interest to disclose.

Additional information

Funding

This work was supported by the Deputy of Research and Technology, Hamadan University of Medical Science, Hamadan, Iran under grant number 9611177273.