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.
Read more
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.