Protocol

Mitochondrial Medicine

Volume 1265 of the series Methods in Molecular Biology pp 103-112

Formulation and Optimization of Mitochondria-Targeted Polymeric Nanoparticles

  • Sean MarracheAffiliated withNanoTherapeutics Research Laboratory, Department of Chemistry, University of Georgia
  • , Rakesh K. PathakAffiliated withNanoTherapeutics Research Laboratory, Department of Chemistry, University of Georgia
  • , Shanta DharAffiliated withNanoTherapeutics Research Laboratory, Department of Chemistry, University of GeorgiaDepartment of Chemistry, University of Georgia Email author 

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Abstract

Targeted delivery of therapeutics to the mitochondria of cells without alteration of drug properties can be a vital technique in the treatment of a variety of mitochondrial-dysfunction-related diseases. Herein, we describe a detailed protocol for synthesis and characterization of a functionalized polymer to build mitochondria-targeted nanoparticles (NPs). The block polymer was decorated with a lipophilic triphenylphosphonium (TPP) cation for mitochondrial trafficking of payload-loaded polymeric NPs. TPP-based lipophilic cations have the ability to cross the mitochondrial membrane. A mitochondria-targeted block copolymer poly(dl-lactide-co-glycolide)-b-polyethylene glycol-TPP and a nontargeted poly(dl-lactide-co-glycolide)-b-polyethylene glycol polymer were synthesized and their NPs were prepared. A nanoprecipitation method combined with polymer blending technology was adopted in order to get suitable size and charged NPs for efficient mitochondrial trafficking.

Key words

Biodegradable polymeric nanoparticles Poly(dl-lactide-co-glycolide) Mitochondria Triphenylphosphonium cation Nanoprecipitation Polymer blending