A Nanoemulgel for Nose-to-Brain Delivery of Quetiapine - QbD-Enabled Formulation Development &In-vitro Characterization

Second-generation antipsychotics, quetiapine hemifumarate (QF), exhibited highly active against negative and positive signs of psychosis. However, contemporary reports have shown that long-term therapy with QF causes lethal thrombocytopenia and leukopenia. Hence, to circumvent the drawbacks of available therapies, the current work aimed to design a QF-loaded biodegradable nanoemulsion (QF-NE) with suitable surface charge modification by poloxamer-chitosan and evaluate its targeting efficiency against RPMI-2650 cell lines. QF-loaded poloxamer-chitosan in-situ gel (QF-Nanoemulgel) was formulated through the O/W emulsification aqueous titration technique and optimized using the QbD approach. Optimized QF-Nanoemulgel subjected to evaluate for globule size, PDI, zeta potential, %T, viscosity, %EE, and ex-vivo mucoadhesive strength were found to be 15.0±0.3 nm, 0.05±0.001, -18.3±0.2 mV, 99.8±0.8%, 13.5±2.1 cP, 69.0±1.5%, and 43.7±1.5 g, respectively. QF-Nanoemulgel revealed sustained release and obeyed zero-order kinetics compared to QF-NE and QF-suspension. Additionally, nanoformulations treated blood samples did not cause hemolytic activity compared to drug and negative control after 10 h treatment. Further, in-vitro cytotoxicity, cellular uptake, and permeation of 12.5 and 25 μM QF-Nanoemulgel were assessed on RPMI-2650 cells and discovered nontoxic with 0.55±0.02 µg and 1.1±0.04 µg cellular permeation, respectively, which ensured the safety and potency of QF-Nanogel. Current research revealed the successful development of intranasal QF-Nanoemulgel as a novel dosage form for the safe and effective delivery of QF in schizophrenia patients.

Cellular permeation; Chitosan Nanoemulgel; Mental disorders; Nose-to-brain delivery; Quetiapine; RPMI-2650 cells; Transepithelial electrical resistance.