A potential means of pharmacological management of
ischemic stroke is rapid intervention using potent
neuroprotective agents.
Thyroid hormone (T3) has been shown to protect against ischemic damage in
middle cerebral artery occlusion (MCAO) model of ischemic brain
stroke. While
thyroid hormone is permeable across the blood-brain barrier, we hypothesized that efficacy of
thyroid hormone in ischemic brain
stroke can be enhanced by encapsulation in nanoparticulate delivery vehicles. We tested our hypothesis by generating
poly-(lactide-co-glycolide)-polyethyleneglycol (
PLGA-b-PEG) nanoparticles that are either coated with
glutathione or are not coated. We have previously reported that
glutathione coating of PLGA-PEG nanoparticles is an efficient means of brain targeted
drug delivery. Encapsulation of T3 in PLGA-PEG delivery vehicle resulted in particles that were in the nano range and exhibited a zeta potential of -6.51 mV (uncoated) or -1.70 mV (coated). We observed that both
glutathione-coated and uncoated nanoparticles are taken up in cells wherein they stimulated the expression of
thyroid hormone response element driven reporter robustly. In MCAO model of
ischemic stroke, significant benefit of administering T3 in nanoparticulate form was observed over injection of a T3
solution. A 34 % decrease in tissue
infarction and a 59 % decrease in
brain edema were seen upon administration of T3
solution in MCAO
stroke model. Corresponding measurements for uncoated T3 nanoparticles were 51 % and 68 %, whereas for the
glutathione coated were 58 % and 75 %. Our study demonstrates that using nanoparticle formulations can significantly improve the efficacy of
neuroprotective drugs in ischemic brain
stroke.