Mitochondria-targeted drug delivery in neurodegenerative diseases

Abstract Mitochondria play a crucial role in eukaryotic cells not only in energy molecule, adenosine triphosphate (ATP), production through the electron transport chain (ETC), it also regulates the redox homeostasis and cell survival. Mitochondria dysfunction and the associated oxidative stress is implicated as disease aggravating mechanisms in neurodegenerative diseases like Parkinson’s Disease, Alzheimer's disease, Huntington’s disease, and amyotrophic lateral sclerosis etc. The unique bilayered structure and high negative potential of mitochondria and also the blood brain barrier penetration capacity of conventional molecules becomes limitation to exert their effects directly to brain mitochondria. Specialized nano formulations are reported to be capable of overcoming these limitations offering sustained and mitochondria specific delivery, further enhancing the pharmacokinetic and biodistribution of the drug(s). Delivery of drugs to mitochondrial is achieved using various systems such as DQAsomes (Dequalinium chloride), a mitochondriotropic nano formulation, and other formulations liposomes, dendrimers, polymeric and metal nanoparticles modified by mitochondriotropic moieties like triphenylphosphonium (TPP). These nanoparticles possess specific particle sizes, with lipophilic surface and desired charges that can penetrate the mitochondrial barrier efficiently. This chapter is summarizes the current strategies employed in mitochondrial drug delivery in neurodegenerative diseases addressing the limitations, clinical and regulatory challenges.