Comparative evaluation of intranasally delivered quetiapine loaded mucoadhesive microemulsion and polymeric nanoparticles for brain targeting: pharmacokinetic and gamma scintigraphy studies

Abstract

Abstract Background Treatment in neurological disorders like schizophrenia requires continuous presence of drug in the brain for a prolonged period of time to achieve an effective therapeutic response. Delivery of antipsychotic drug quetiapine in the form of conventional delivery systems suffers from low oral bioavailability, first-pass metabolism, and frequent dosing. In addition to that biological obstacles present at the brain interface also hinders the transport of quetiapine across the brain. In the present study, nasal delivery of quetiapine loaded nanoparticles and microemulsion formulation were designed to evaluate their individual in vivo potential to achieve brain targeting. Chitosan-based polymeric nanoparticles and mucoadhesive microemulsion systems were developed through ionic gelation and water titration method respectively. Results Microemulsion showed globule size lower than 50 nm with 95% drug loading while, nanoparticles exhibited 65% drug loading with particle size of 131 nm. Nasal diffusion study showed highest diffusion with chitosan-based mucoadhesive microemulsion over nanoparticles suggesting permeation-enhancing effects of chitosan. Due to the overall hydrophilic nature, quetiapine-loaded nanoparticles could not diffuse superiorly across nasal mucosa, hence, showed 1.3 times lesser diffusion compared to mucoadhesive microemulsion. Pharmacokinetics in rats showed highest brain concentration and 1.9-folds higher nasal bioavailability with mucoadhesive microemulsion over nanoparticles suggesting direct brain transport through olfactory route bypassing blood-brain barrier. Conclusion Higher quetiapine transport with mucoadhesive microemulsion suggested that synergistic effects like tight junction modulation by chitosan and unique composition facilitating smaller globule size could be responsible for higher brain transport. Imaging study by gamma scintigraphy also supported pharmacokinetic outcomes and concluded that mucoadhesive microemulsion could be a promising nanocarrier approach for non-invasive nose to brain delivery. Graphical abstract

Keywords

• Brain targeting
• Intranasal delivery
• Quetiapine
• Polymeric nanoparticles
• Mucoadhesive microemulsion
• Gamma scintigraphy