Poly(amidoamine) polymers : soluble linear amphiphilic drug-delivery systems for genes, proteins and oligonucleotides

A review. Polymer--drug and polymer--protein conjugates are emerging as a robust and well-characterized class of therapeutic entity. Although there are no low-mol.-wt. sol. polymer conjugates in routine clin. use, there are many examples of routinely used high-mol.-wt. drugs conjugated to sol. polymers (e.g., Oncospar). Advances in synthetic polymer chem. have fostered the development of linear poly(amidoamine)s (PAA)s that impart both biodegradability, 'smart' (pH responsive) biol. activity and biocompatibility. In their linear form, such as hyper-branched poly(amidoamine) (PAMAM) dendrimers, linear PAAs can be used to deliver large therapeutic entities such as peptides, proteins and genes to either the cytosol or nucleus. Furthermore, these polymers offer great potential in vivo due to their ability to either target the liver or be directed away from the liver and enter tumor mass via the enhanced permeability and retention (EPR) effect. PAAs also exhibit minimal toxicity (dependent upon backbone chem.), relative to well-characterized polymers used for gene delivery. The propensity of PAAs to modulate intracellular trafficking resulting in their cytosolic translocation has also recently been quantified in vivo and is the primary focus of this article