Formulation and Optimization of Mitochondria-Targeted Polymeric Nanoparticles

  • Sean Marrache
  • Rakesh K. Pathak
  • Shanta Dhar
Part of the Methods in Molecular Biology book series (MIMB, volume 1265)


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 



This work was supported by National Institutes of Health start-up Grant (P30 GM 092378) to the University of Georgia (UGA), and by the Office of the Vice President for Research, UGA (S.D.).


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Sean Marrache
    • 1
  • Rakesh K. Pathak
    • 1
  • Shanta Dhar
    • 1
    • 2
  1. 1.NanoTherapeutics Research Laboratory, Department of ChemistryUniversity of GeorgiaAthensUSA
  2. 2.Department of ChemistryUniversity of GeorgiaAthensUSA

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