title: Formulation of 20(S)-protopanaxadiol nanocrystals to improve oral bioavailability and brain delivery.
abstract: 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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Chinese Academy of Medical Sciences, Peking Union Medical College Institute of Medicinal Plant Development, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Wang
authors.affiliation: Chinese Academy of Medical Sciences, Peking Union Medical College Institute of Medicinal Plant Development, China.
authors.forename: Fangrui
authors.initials: F
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Miao
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.
authors.forename: Tongkai
authors.initials: T
authors.lastname: Chen
authors.affiliation: Chinese Academy of Medical Sciences, Peking Union Medical College Institute of Medicinal Plant Development, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China. Electronic address: yzheng@umac.mo.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry*; D065546:Drug Liberation; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D051381:Rats; D012502:Sapogenins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D012995:Solubility
chemical_list: D004337:Drug Carriers; D012502:Sapogenins; C062916:protopanaxadiol
keywords: 20(S)-Protopanaxadiol; Bioavailability; Brain delivery; Nanocrystals; d-α-Tocopheryl polyethylene glycol 1000 succinate