BBB Permeability and Cytotoxic Profiles of Tea Phytoconstituents via Nanoliposomes

Tea-derived phytoconstituents hold promise for neurotherapeutics, but their clinical application is severely limited by poor blood-brain barrier (BBB) penetration and potential cytotoxicity. Unmodified phytochemicals such as theaflavin and quercetin exhibit negligible BBB delivery (<2%) and require high, toxic doses to achieve neuroprotective effects. We encapsulated six tea bioactives, gallic acid, caffeine, chlorogenic acid, quercetin, EGCG, and theaflavin, into nanoliposomes (phosphatidylcholine/cholesterol = 3:1), creating stable nanovesicles (42.6-85.3 nm, zeta potential 28.6 to -57.2 mV) designed to enhance brain delivery. Encapsulation efficiencies ranged from 51.4% (theaflavin) to 87.8% (caffeine). Cytotoxicity assays (MTT, 100-500 μM) showed EGCG and caffeine were safe, while chlorogenic acid, theaflavin, and quercetin exhibited dose-dependent toxicity, with liposome encapsulation shifting IC_{5 0} values by over 2-fold. BBB permeability assessed via DAPI fluorescence and HPLC in zebrafish brains revealed gallic acid uptake of 17.54 ± 0.04%, moderate uptake for caffeine and minimal uptake (∼1.44 ± 0.70%) for theaflavin and quercetin. Nanoliposome encapsulation substantially enhances encapsulation efficiency and brain delivery of tea phytochemicals, achieving up to a 10-20-fold increase in BBB uptake and reducing cytotoxicity by more than 50%. These findings highlight a promising neurotherapeutic and nutraceutical developmental strategy.