Protective effects of cationic bovine serum albumin-conjugated PEGylated tanshinone IIA nanoparticles on cerebral ischemia.

Abstract

Tanshinone IIA is a good candidate for treating cerebral ischemia, but its short half-life and poor permeability across the blood-brain-barrier (BBB) limit its curative efficacy. In this study, we successfully developed cationic bovine serum albumin-conjugated tanshinone IIA PEGylated nanoparticles (CBSA-PEG-TIIA-NPs). A cerebral ischemia rat model was established to evaluate the treatment efficacy and protective mechanism of CBSA-PEG-TIIA-NPs. CBSA-PEG-TIIA-NPs showed the mean particle size 118 ± 14 nm with drug loaded ratio and encapsulation efficiency 5.69 ± 0.6% and 83.2 ± 2.6%, respectively. The pharmacokinetics demonstrated that CBSA-PEG-TIIA-NPs could significantly prolong circulation time and increase plasma concentration compared with intravenously administrated TIIA solution. The biodistribution and brain uptake study confirmed that CBSA-PEG-TIIA-NPs possessed better brain delivery efficacy with a high accumulation in brain. CBSA-PEG-TIIA-NPs obviously ameliorated infarct volume, neurological deficit and histopathological severity. Treatment with CBSA-PEG-TIIA-NPs markedly inhibited the levels of the MPO, TNF-α, IL-1β and IL-6. Furthermore, CBSA-PEG-TIIA-NPs significantly decreased the mRNA expressions of iNOS and p38MAPK, upregulated PPARγ expression, and inhibited the protein levels of iNOS, GFAP and p38MAPK phosphorylation. These results demonstrated that CBSA-PEG-TIIA-NPs possessed remarkable neuroprotective effects on ischemic stroke through modulation of inflammatory cascades and neuronal signal pathways involved in cerebral ischemia.

• Authors: Xin Liu, Chiying An, Peng Jin, Xuesong Liu, Longhu Wang
• Journal: Biomaterials (Biomaterials) Vol. 34 Issue 3 Pg. 817-30 (Jan 2013) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 23111336 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Abietanes
• Drug Carriers
• Immunosuppressive Agents
• Interleukin-1beta
• Interleukin-6
• PPAR gamma
• Tumor Necrosis Factor-alpha
• tanshinone
• Serum Albumin, Bovine
• Polyethylene Glycols
• p38 Mitogen-Activated Protein Kinases

Topics

• Abietanes (administration & dosage, pharmacokinetics, therapeutic use)
• Animals
• Brain (drug effects, immunology, metabolism, pathology)
• Brain Ischemia (drug therapy, genetics, immunology, pathology)
• Cattle
• Drug Carriers (chemistry)
• Gene Expression Regulation (drug effects)
• Immunosuppressive Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Interleukin-1beta (immunology)
• Interleukin-6 (immunology)
• Nanoparticles (chemistry, ultrastructure)
• PPAR gamma (genetics)
• Polyethylene Glycols (chemistry)
• Rats
• Rats, Sprague-Dawley
• Serum Albumin, Bovine (chemistry)
• Tumor Necrosis Factor-alpha (immunology)
• p38 Mitogen-Activated Protein Kinases (genetics)