Exploring the effect of intramuscularly injected polymer/lipid hybrid nanoparticles loaded with quetiapine fumarate on the behavioral and neurological changes in cuprizone-induced schizophrenia in mice

The current study intended to develop a new treatment of schizophrenia having a sustained release activity. Quetiapine fumarate (QF)-loaded polymer/lipid hybrid nanoparticulate systems of polycaprolactone (PCL) and Geleol™ were fabricated using polyvinyl alcohol (3% w/v). The proposed hybrid systems were formed conducting the emulsion/solvent evaporation procedure followed by evaluating their size, entrapment efficiency and in-vitro QF release. An optimum formulation (HF-G3; composed of PCL: Geleol™ in ratio 1:1 w/w) demonstrated small particle size (313 ± 8.59 nm) and high entrapment efficiency-values (99.68 ± 0.10%) and thus was selected for further studies. A sustained release profile was attained from the studied formulation where about 95% QF was released at 28 days.

Highlights

• Quetiapine fumarate shows limited oral bioavailability (9%).

• Polymer/lipid hybrid nanoparticles have enhanced therapeutic effects.

• Cuprizone is used to induce schizophrenia-like behaviors.

• Lipoid S75 was used as a co-surfactant along with PVA.

• The developed formulation reduced levels of cytokines besides GABA and GFAP.

This study aims to assess the neuroprotective influence of the intramuscularly injected formulation (HF-G3) against cuprizone (CPZ)-induced schizophrenia in Swiss mice. Mice had CPZ (0.2%) in their diet for 21 days to induce schizophrenia. Mice were allocated into 4 groups: normal control, CPZ-fed, QF-treated and HF-G3/treated (10 mg/kg; twice per week) for 3 weeks. The behavioral alterations, the amounts of pro-inflammatory cytokines TNF-α and IL-1β besides the levels of glial fibrillary acidic protein (GFAP) and gamma-aminobutyric acid (GABA) were evaluated between the four groups. Results revealed the success of the optimum formulation in ameliorating the CPZ-induced behavioral disorders as well as in reducing the levels of cytokines, GABA and GFAP.

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Nermeen A. Elkasabgy, Abeer Salama, Alaa H. Salama, Exploring the effect of intramuscularly injected polymer/lipid hybrid nanoparticles loaded with quetiapine fumarate on the behavioral and neurological changes in cuprizone-induced schizophrenia in mice, Journal of Drug Delivery Science and Technology,
2022, 104064, ISSN 1773-2247,
https://doi.org/10.1016/j.jddst.2022.104064.