Intracellular Targeted Delivery

Maruyama, K. Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Adv. Drug Deliv. Rev. 2011, 63 (3), 161-169. 

Synthetic Polymers. Synthetic polymers are versatile and offer promise for both targeting and extracellular-intracellular drug delivery. Of the many soluble synthetic polymers known, the poly(amino acids) [poly(L-lysine), poly(L-aspartic acid), and poly(glutamic acid)], poly(hydroxypropylmethacrylamide) copolymers (polyHPMA), and maleic anhydride copolymers have been investigated extensively, particularly in the treatment of cancers. A brief discussion of these materials is presented. 

Caveolae-Linked Endocytosis and Non-Caveolae, Clathrin-Independent Endocytotsis Offer Delivery of Drugs to Novel Intracellular Targets... 

Recently, new classes of proteins that are responsible for the homeostasis of copper and for its delivery to specihc intracellular targets have been identified. Copper cannot be present as the free ion in solution as its high reactivity leads to the production of radicals. It appears always to be bound to some proteins and is present as copper(I) due to the reducing conditions of the cell environment. Small soluble proteins, called copper chaperones (see chapter by Elam et al., this volume), function to shuttle copper to specihc target proteins. Other large, membrane-bound proteins are present to pump copper from one cell compartment to another. 

An interesting example of intracellular targeting of liposomes was described recently, when liposomes containing in their membrane composition mitochonriotropic amphiphilic cation with delocalized positive charge were shown to specifically target mitochondria in inact cells (153). The liposomes were deemed mitochondriotropic due to inclusion of lipidic analogues of triphenylphosphonium cations, which facilitates the efficient subcellular delivery of proapototic ceramide to mitochondria of mammalian cells and improves its activity in vitro and in vivo (154). 

Efficacy of therapeutically active drugs known to act on intracellular targets can be enhanced by specific delivery to the site of action. Triphenylphosphoniiun cations can be used to create subcellular targeted Hposomes that efficiently deliver drugs to mitochondria, thus enhancing their therapeutic action. 

Typically, the processed polymeric nanoparticles are stable in the blood stream and elsewhere in the body [20]. Their degradation and drug release are determined by the chemical degradation rate of the polymer such as poly(lactide) and poly(glycolide). Such nanopartides can be used for site-spedfic intracellular drug delivery if they have targeting moieties on the surface. 

Identification of new target molecules to assist intracellular antibody delivery... 

Identification of New Target Molecules to Assist Intracellular Antibody Delivery... 

By nature, the nucleic acid therapeutics have a high negative charge density and are enzymatically labile hydrophilic biomacromolecules thus, efficient delivery of these therapeutics faces similar challenges as the peptide and protein therapeutics. Irrespective of whether the nucleus (in the case of DNA delivery) or the cytoplasm (e.g., for siRNA delivery) of the cell is the intracellular target site, protection and targeting approaches are required to efficiently deliver the drug. 

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