4.26 pH-Responsive Polymers for the Intracellular Delivery of Biomolecular Drugs

摘要: There is significant potential for intracellular-acting biologics as therapeutics, but requirement of effective methods delivery has limited their clinical use. Applications biomacromolecular drugs are diverse and include nonviral gene therapy, knockdown with short interfering RNA, antigen vaccines, peptide/protein inhibitors. To be relevant these purposes, biomacromolecule carriers must provide stability against enzymatic degradation, targeted to internalized by the desired cell type, result in intracellular trafficking environment where target located, present drug a bioactive conformation once site reached. Because relatively large molecular weight hydrophilicity biologic molecules, they cannot readily diffuse through lipid bilayer membranes. Instead, biomacromolecules endocytosis, which sequesters them into endolysosomal vesicles results exocytotic recycling or lysosomal degradation. In this chapter, multiple classes polymers discussed that utilize pH-driven activity disrupt escape endolysosomes order access targets. The basic mechanisms membrane disruption recent applications detailed anionic ‘encrypted’ physically bilayers, cationic amine-containing function proton sponges, pore-forming fusogenic peptides.