Formulation of 20(S)-protopanaxadiol nanocrystals to improve oral bioavailability and brain delivery.
The aim of this study was to fabricate 20(S)-protopanaxadiol (PPD) nanocrystals to improve PPD's oral bioavailability and brain delivery. PPD nanocrystals were fabricated using an anti-solvent precipitation approach where d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was optimized as the stabilizer. The fabricated nanocrystals were nearly spherical with a particle size and drug loading of 90.44 ± 1.45 nm and 76.92%, respectively. They are in the crystalline state and stable at 4°C for at least 1 month. More than 90% of the PPD could be rapidly released from the nanocrystals, which was much faster than the physical mixture and PPD powder. PPD nanocrystals demonstrated comparable permeability to solution at 2.52 ± 0.44×10(-5)cm/s on MDCK monolayers. After oral administration of PPD nanocrystals to rats, PPD was absorbed quickly into the plasma and brain with significantly higher Cmax and AUC0-t compared to those of the physical mixture. However, no brain targeting was observed, as the ratios of the plasma AUC0-t to brain AUC0-t for the two groups were similar. In summary, PPD nanocrystals are a potential oral delivery system to improve PPD's poor bioavailability and its delivery into the brain for neurodegenerative disease and intracranial tumor therapies in the future.
['Chen|Chen|C|', 'Wang|Lisha|L|', 'Cao|Fangrui|F|', 'Miao|Xiaoqing|X|', 'Chen|Tongkai|T|', 'Chang|Qi|Q|', 'Zheng|Ying|Y|']
D000284:Administration, Oral D000818:Animals D001682:Biological Availability D001921:Brain D002626:Chemistry, Pharmaceutical D004285:Dogs D004337:Drug Carriers D065546:Drug Liberation D061985:Madin Darby Canine Kidney Cells D008297:Male D053758:Nanoparticles D010316:Particle Size D051381:Rats D012502:Sapogenins D012995:Solubility
20(S)-Protopanaxadiol Nanocrystals Bioavailability Brain delivery d-α-Tocopheryl polyethylene glycol 1000 succinate