ABSTRACT
In recent years, mitochondria have gained signicant attention from researchers due to their specic role in various physiological and cellular processes. It has also been reported that mitochondria play a critical role in liver diseases and, thus, have also been considered a potential target to treat liver diseases. Mitochondria, being cellular organelles, are located in the cell cytoplasm, which makes drug entry into mitochondria a challenging task due to the presence of various biological barriers. Therefore,
Abstract .................................................................................................................. 169 Introduction ............................................................................................................ 170 Drug Delivery to Mitochondria: Exploiting the Physiological Characteristics of Mitochondria ..................................................................................................... 170
Mitochondrial Membrane Potential .................................................................. 171 Mitochondrial Protein Import Machinery ......................................................... 172
Strategies for Drug Delivery to Mitochondria ....................................................... 174 Mitochondriotropics .......................................................................................... 174 Conjugation to the Mitochondrial Leader Sequence/MitochondrialTargeting Signal ................................................................................................ 178
Novel Carrier Systems for Mitochondrial Delivery of Therapeutics ..................... 179 DQAsome: A Mitochondria-Selective Vesicular System .................................. 179 Liposomes as Mitochondriotropic Carriers ....................................................... 181 DF-MITO-Porter: A Nanocarrier for Mitochondrial Delivery via a Stepwise Membrane Fusion Process ................................................................. 182 Polymeric Nanoparticles for Mitochondrial Delivery of Therapeutics ............. 184
Cell-/Organ-Selective Mitochondrial Targeting: Liver Targeting .......................... 186 Conclusion ............................................................................................................. 187 References .............................................................................................................. 188
several strategies have been designed to combat these barriers and to specically target mitochondria, which include direct drug modication and encapsulation of drugs in novel carriers. Further, to increase cell specicity, these carriers can also be modied with ligands specic to cell surface receptors. In this chapter, we discuss mitochondrial properties which are exploited to develop novel approaches and compile studies involving the use of these approaches for the delivery of drugs/DNA to the mitochondria. We also discuss cell-specic delivery systems to target mitochondria of liver cells, speci- cally for the treatment of liver diseases related to mitochondrial dysfunction.
