Phospholipid-based nano drug delivery system of curcumin using MSP1D1 protein and poloxamer 407: a comparative study for targeted drug delivery to the brain

This study aims to investigate a potential alternative for MSP1D1 protein to develop a lipid polymer hybrid nanoparticle (LPHN) system of curcumin using poloxamer 407 and its targeted drug delivery to the brain. Design of experiment (DoE) was used to optimize the lipid nanodisc and LPHN delivery system of curcumin by the thin film hydration method. Solid-state characterization of the optimized lipid nanodiscs and LPHNs was performed using DLS, TEM, SEM, PXRD, and DSC. In vitro release, stability study, and in vivo anti-inflammatory and bioavailability studies in mice brains were performed for the optimized LPHN delivery system. DLS and microscopic data showed that the average sizes of the lipid nanodisc and LPHN systems were 125-198 nm and 135-240 nm, respectively. The LPHN delivery system of curcumin exhibited high entrapment efficiency (95.7 +/- 2.2%) compared to lipid nanodiscs (91.2 +/- 1.7%). In vitro release data showed slow release of lipid nanodiscs and LPHN systems, particularly after 72 h (47.6% and 37.6%, respectively). Stability data indicated that the LPHN delivery system of curcumin was stable after 3 months, while significant growth in size was observed for lipid nanodiscs. PXRD and DSC results showed the partial amorphization of the LPHN system. In vivo anti-inflammatory data suggested that curcumin has anti-inflammatory activity when delivered as an LPHN system. In vivo bioavailability study showed curcumin (6.3 ng/mL) in brain homogenates of mice treated with the LPHN delivery system, suggesting its potential for targeting the brain to treat neurodegenerative diseases.