Synthesis, properties and applications of second generation polyamidoamines.

Poly(amidoamine)s (PAAs) are synthetic biodegradable polymers that can be designed to be highly biocompatible. They are obtained by stepwise Michael-type polyaddition of primary or secondary amines to bisacrylamides and contain tert-amine and amide groups regularly arranged along the polymer chain. By employing functional monomers, a number of additional functions may be added, including peptide and sugar moieties. PAAs were first described in 1970. Subsequently, their physicochemical and biological properties were reviewed at intervals. Several PAAs have been shown to possess a remarkable potential for biomedical applications in that they are biodegradable and biocompatible, and owing to their versatility can be tailored to specific applications. As a rule, PAAs are water soluble and all of them show different charge distribution profiles as a function of pH. In regard to biocompatibility, most PAAs exhibit LD50 values in vitro higher by 2 orders of magnitude than PLL, PEI, or PAMAM dendrimers. In particular, amphoteric PAAs that in extra cellular fluids (pH ≈7.4) are zwitterionic, but predominantly anionic, are highly biocompatible and exhibit a “stealth-like” behavior, that is, after intravenous injection in test animals are not captured by the reticulo-endothelial system and have a prolonged permanence in the blood circle. In tumor-bearing animals they are passively concentrated in the tumor tissues by the so called EPR (Enhanced Permeation and Retention) effect. PAAs may be obtained either as water-soluble products, or as cross-linked hydrogels. Novel examples of polymer derivatives tailored for specific therapeutic applications in the field of nanomedicine and drug delivery based on polyamidoamines are reported in this abstract. In particular, water-soluble second generation PAAs warrant potential, inter alia, as cell adhesion promoters, non-toxic carriers for bioactive protein and nucleic acids both in vitro and in vivo and powerful antiviral agents with negligible toxicity towards healthy cells. As cross-linked hydrogels they can be used as scaffolds for tissue engineering: for instance, they recently proved successful as bioeliminable tubular conduits for peripheral nerve regeneration after implantation in vivo. On the other side, biotechnological applications do not exhaust the potential of PAAs for practical exploitation. For example, some PAAs are presently being investigated as selective absorbers of traces of nasty inorganic ions from waters for human use; copolymers of PAAs with ,  and -cyclodextrins can absorb inorganic and organic pollutants in a single step; hybrid products with polysaccharides such as chitosan, cellulose, dextran and others have been prepared.