Investigation On Targeted Nasal In Situ Gel Solid Lipid Nanoparticles Loaded Quetiapine Fumarate

Objective: To prepare nasal in situ gel solid lipid nanoparticles loaded Quetiapine fumarate. We used the(+)MK-801 to prepara of rat model of schizophrenia and to exam the related properties and a preliminary study on the brain targeting.Methods:1 The prescription process study of nasal in situ gel solid lipid nanoparticles loaded Quetiapine fumarateUtilizing microemulsion method for formulat solid lipid nanoparticles loaded Quetiapine fumarate(QF-SLN) were prepared by Glycerin monostearate. Using central composite design and response surface method to optimize the thermosensitive nasal in situ gel with P407 and P188.2 The related properties investigate of nasal in situ gel solid lipid nanoparticles loaded Quetiapine fumarateThe size and the potential distribution of nasal in situ gel solid lipid nanoparticles loaded Quetiapine fumarate. HPLC method and Ultrafiltration centrifugal tube method were used to investigate the entrapment efficiency(EE%) of nasal in situ gel solid lipid nanoparticles loaded Quetiapine fumarate. Drug stability test chamber was used to examine the stability of nasal in situ gel solid lipid nanoparticles loaded Quetiapine fumarate.3 Inverstigation on brain targeting property of nasal in situ gel solid lipid nanoparticles loaded Quetiapine fumarate in schizophrenia model ratsPharmacokinetic study of Quetiapine fumarate in rats. The(+)MK-801 was applied to rats to establish schizophrenia’s models. Examine drug concentration after the treatment about quetiapine fumarate flat nasal solid lipid nanoparticle nasal in situ gel in model rats. HE staining were observed before and after building the rat hippocampal tissue pathology change.Results:1. The formulation of solid lipid nanoparticlesl is most at Km=1:9, the21% P407, 5.6% P188 conform to the phase transition temperature of the gel prescription nasal drug delivery.2. The particle size of nasal in situ gel solid lipid nanoparticles loaded Quetiapine fumarate was(136.3±6.393)d.nm, the Zeta was(35.2±0.794)m V, the EE% was 97.60±0.48%.3. The nasal in situ gel solid lipid nanoparticles loaded Quetiapine fumarate stable in high temperature,strong light conditions were stably. It needs a cool preservation.4. With dose in situ gel nasal drug delivery than API lavage after dosing drug concentration in plasma and brain tissue were significantly improved. And there is no significant difference with tail intravenous drug group.Conclusions:The nasal in situ gel solid lipid nanoparticles loaded Quetiapine fumarate has a good brain targeting,it can provide a new drug delivery ways and treatment methods for clinical treatment of schizophrenia.