Tailoring the efficacy of nimodipine drug delivery using nanocarriers based on A2B miktoarm star polymers

We report a nanocarrier based on A2B type miktoarm polymers (A=polyethylene glycol (PEG); B=polycaprolactone (PCL)) for nimodipine (NIM), a hydrophobic drug with very poor aqueous solubility that is commonly prescribed for the prevention and treatment of delayed ischemic neurological disorders. The A2B star polymers were constructed on a core with orthogonal functionalities that facilitated the performance of " click" chemistry followed by ring-opening polymerization. These star polymers assemble into spherical micelles into which NIM can be easily loaded by the co-solvent evaporation method. The micelles obtained from the star polymer PEG7752-PCL5800 showed NIM encapsulation efficiency of up to 78wt% at a feed weight ratio of 5.0%. The loading efficiency of the micelles was dependent on the length of the PCL arm in the A2B miktoarm polymers. Aqueous solubility of NIM was increased by ∼200 fold via micellar encapsulation. The in vitro release of NIM from the micelles was found to occur at a much slower rate than from its solution. Lipopolysaccharide induced nitric oxide production in N9 microglia cells was reduced in the presence of micelle-encapsulated NIM, as well as in the presence of micelles alone. The treatment of microglia with micelle-encapsulated NIM reduced the release of TNF-α, a pro-inflammatory cytokine. These results suggest that NIM-loaded miktoarm micelles could be useful in the treatment of neuroinflammation. © 2010 Elsevier Ltd.