alexa Tailoring the efficacy of nimodipine drug delivery using nanocarriers based on A2B miktoarm star polymers.
Materials Science

Materials Science

Journal of Nanomedicine & Biotherapeutic Discovery

Author(s): Soliman GM, Sharma R, Choi AO, Varshney SK, Winnik FM, , Soliman GM, Sharma R, Choi AO, Varshney SK, Winnik FM, , Soliman GM, Sharma R, Choi AO, Varshney SK, Winnik FM, , Soliman GM, Sharma R, Choi AO, Varshney SK, Winnik FM,

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Abstract We report a nanocarrier based on A(2)B 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 A(2)B 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 PEG775(2)-PCL5800 showed NIM encapsulation efficiency of up to 78 wt\% 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 A(2)B miktoarm polymers. Aqueous solubility of NIM was increased by approximately 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-alpha, a pro-inflammatory cytokine. These results suggest that NIM-loaded miktoarm micelles could be useful in the treatment of neuroinflammation. Copyright (c) 2010 Elsevier Ltd. All rights reserved. This article was published in Biomaterials and referenced in Journal of Nanomedicine & Biotherapeutic Discovery

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