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

Biomaterials. 2012 Oct 27;

Authors: Liu X, An C, Jin P, Liu X, Wang L


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.

PMID: 23111336 [PubMed - as supplied by publisher]