- Title
-
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.
- Source
- Full text @ Int. J. Nanomedicine
Figure 1 GB-NPs characterization. (A) Size distribution. Insert: TEM image. Scale bar: 100 nm. (B) Zeta potential. (C) DSC profiles. (D) In vitro release profiles. |
Figure 2 Analysis of C6-NPs uptake and intracellular trafficking in MDCK cells. (A) C6-NPs were visualized within cells following treatment with endocytosis inhibitors (MβCD: methyl-β-cyclodextrin, CPZ: chlorpromazine, HS: hypertonic sucrose, EIPA: 5-(N-ethyl-N-isopropyl)-amiloride). Scale bar: 25 μm. (B) C6-NPs cellular uptake was quantified (n=3). *p<0.05, ***p<0.001 vs the Control group. (C) The co-localization of C6-NPs with lysosomes (Lyso), endoplasmic reticulum (ER), and mitochondria (Mito) was visualized using appropriate tracking dyes. Scale bar: 25 μm. |
Figure 3 (A) MTT assays in response to the indicated treatments (n=3). (B) GB-NPs protected against MPP+-mediated cytotoxicity (n=3). ***p<0.001 vs the MPTP group. ##p<0.01 vs the GB group. |
Figure 4 C6-NPs were used to treat 7 dpf zebrafish larvae. Blue, yellow and red arrows are used to mark the eyes, brain and digestive system, respectively. Scale bar: 500 μm. |
Figure 5 Plasma and brain pharmacokinetic profiles of GB and GB-NPs in rats. (A) Plasma concentration-time profile (n=6). (B) Brain concentration-time profile (n=4). |
Figure 6 Schematic overview of the mechanisms governing the absorption and accumulation of GB-NPs following oral uptake. |
Figure 7 The impact of GB-NPs on behavioral impairment in PD model mice. A pole test on days 3 and 5 post-MPTP injection (A, B) and a rotarod test on days 4 and 6 post-MPTP injection (C, D) were conducted (n=8). (E) Representative activity traces (green) derived from video tracking. Total distance traveled (F) and average speed (G) of treated mice (n=8). *p<0.05, **p<0.01, ***p<0.001 vs the Control group. #p<0.05, ##p<0.01, ###p<0.001 vs the GB group. |
Figure 8 The impact of GB-NPs in PD model mice. (A) Representative images of TH-stained sections of murine brain tissue. Scale bar: 100 μm. (B) Quantification of TH+ neurons (n=5). Striatal DA (C), DOPAC (D) and HVA (E) levels (n=4). *p<0.05 and **p<0.01 vs the MPTP group. #p<0.05 and ##p<0.01 vs the GB group. |