PUBLICATION
Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson's Disease
- Authors
- Zhao, Y., Xiong, S., Liu, P., Liu, W., Wang, Q., Liu, Y., Tan, H., Chen, X., Shi, X., Wang, Q., Chen, T.
- ID
- ZDB-PUB-210101-17
- Date
- 2020
- Source
- International Journal of Nanomedicine 15: 10453-10467 (Journal)
- Registered Authors
- Keywords
- PD treatment, blood–brain barrier, drug delivery system, endocytosis, zebrafish
- MeSH Terms
-
- Administration, Oral
- Animals
- Biological Availability
- Blood-Brain Barrier/drug effects
- Brain/drug effects
- Dogs
- Embryo, Nonmammalian/drug effects
- Ethylene Glycols/chemistry
- Female
- Ginkgolides/administration & dosage*
- Ginkgolides/pharmacokinetics
- Ginkgolides/pharmacology*
- Humans
- Lactones/administration & dosage*
- Lactones/pharmacokinetics
- Lactones/pharmacology*
- Madin Darby Canine Kidney Cells
- Male
- Mice, Inbred C57BL
- Nanoparticles/administration & dosage*
- Nanoparticles/chemistry
- Neuroprotective Agents/administration & dosage
- Neuroprotective Agents/pharmacology*
- Parkinson Disease/drug therapy*
- Polyesters/chemistry
- Rats, Sprague-Dawley
- Zebrafish/embryology
- PubMed
- 33380795 Full text @ Int. J. Nanomedicine
Citation
Zhao, Y., Xiong, S., Liu, P., Liu, W., Wang, Q., Liu, Y., Tan, H., Chen, X., Shi, X., Wang, Q., Chen, T. (2020) Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson's Disease. International Journal of Nanomedicine. 15:10453-10467.
Abstract
Purpose Ginkgolide B (GB) is a terpene lactone derivative of Ginkgo biloba that is believed to function in a neuroprotective manner ideal for treating Parkinson's disease (PD). Despite its promising therapeutic properties, GB has poor bioavailability following oral administration and cannot readily achieve sufficient exposure in treated patients, limiting its clinical application for the treatment of PD. In an effort to improve its efficacy, we utilized poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) nanoparticles as a means of encapsulating GB (GB-NPs). These NPs facilitated the sustained release of GB into the blood, thereby improving its ability to accumulate in the brain and to treat PD.
Methods and results Using Madin-Darby canine kidney (MDCK) cells, we were able to confirm that these NPs could be taken into cells via multiple nonspecific mechanisms including micropinocytosis, clathrin-dependent endocytosis, and lipid raft/caveolae-mediated endocytosis. Once internalized, these NPs tended to accumulate in the endoplasmic reticulum and lysosomes. In zebrafish, we determined that these NPs were readily able to undergo transport across the chorion, gastrointestinal, blood-brain, and blood-retinal barriers. In a 1-methyl-4-phenylpyridinium ion (MPP+)-induced neuronal damage model system, we confirmed the neuroprotective potential of these NPs. Following oral administration to rats, GB-NPs exhibited more desirable pharmacokinetics than did free GB, achieving higher GB concentrations in both the brain and the blood. Using a murine PD model, we demonstrated that these GB-NPs achieved superior therapeutic efficacy and reduced toxicity relative to free GB.
Conclusion In conclusion, these results indicate that NPs encapsulation of GB can significantly improve its oral bioavailability, cerebral accumulation, and bioactivity via mediating its sustained release in vivo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping