Engineered Novel Brijaluronic Terpesomes for Brain-Targeted Quercetin Delivery: Optimization, Ex Vivo and...

This research focuses on creating a novel Brijaluronic-based terpesomal system capable of transporting quercetin (QER) efficiently to the brain. The vesicles were fabricated through an ethanol-injection method and then refined using a structured optimization approach in Design-Expert® software. The influence of three main formulation parameters: terpene-to-drug ratio, surfactant type, and hyaluronic acid amount were evaluated. The optimization process was designed to maximize EE%, minimize VS, and maintain ZP within an acceptable stability range. The optimal formula hit a desirability target of 0.957. It achieved an 88.66% EE%, featured nano-carriers sized at 72.09 nm, and had a stable charge of - 26.5 mV. Physicochemical characterization studies revealed a spherical morphology, an in-vitro release defined by a biphasic profile, and a secure structural integrity which was validated using FTIR analysis. Moreover, over the course of three months, the formulation did not degrade or change significantly, demonstrating its high degree of stability. Notably, terpesomes demonstrated a ~ 3.5-fold enhancement in antioxidant activity, reducing the IC₅₀ from 12.98 ± 0.82 µg/mL to 3.68 ± 0.20 µg/mL, representing a statistically and pharmacologically significant improvement. Radio-kinetic assessments further supported its potential for precise brain targeting. The brain/blood was highest for the optimized formulation at all-time points. Compared with the nasal QER solution, Technetium-99m ([^99mTc]Tc)-QER-loaded terpesomes exhibited superior brain-targeting efficiency, as evidenced by higher AUC, shorter T_max, and greater C_max values in the brain. Taken together, the Brijaluronic terpesomes represent a highly promising, innovative nano-platform. This engineered system appears poised to boost the effectiveness of QER in neurotherapeutic applications.