Euro Biotechnology 2018 Next step in drug delivery getting inside cells and to individual organelles- Vladimir P Torchilin- Northeastern University

摘要

Many pharmaceutical agents need to be deliveredintracellularly to exert their therapeutic action onto specificcell organelles for maximum therapeutic outcome. It is true forpreparations for gene and antisense therapy (target cell nuclei),proapoptotic drugs, (target mitochondria or lysosomes); orenzymes for therapy of storage diseases (target lysosomes).Intracellular delivery of different biologically-active moleculesis one of the key problems in drug delivery in general. In somecases, intracellular drug delivery allows to overcome seriousproblems, such as multifrug resistance in cancer. The problemhowever is that the lipophilic cell membranes restrict thedirect intracellular penetration of various extracellularcompounds. Under certain circumstances, these molecules oreven small particles can be taken from the extracellular spaceinto cells by the receptor-mediated endocytosis, but anymolecule/particle entering the cell via the endocytic pathwaybecomes entrapped in endosome and eventually ends in thelysosome, where active degradation takes place. As a result,only a small fraction of intact therapeutic substance appears inthe cell cytoplasm and performs its function.