Dendritic Polyamines: Simple Access to New Materials with Defined Treelike Structures for Application in Nonviral Gene Delivery

Abstract

Polycationic dendrimers are interesting nonviral vectors for in vitro DNA delivery. We describe a simple approach to the synthesis of dendritic polyamines with different molecular weights and adjustable flexibility (degrees of branching; DB). Both parameters influence the transfection efficiency and the cell toxicity of the polymer. Functionalization of hyperbranched polyethylenimine (PEI) by a two-step procedure generated fully branched pseudodendrimers (analogues of polypropylenimine (PPI) and polyamidoamine (PAMAM) dendrimers). The DNA transfection efficiencies observed for these polymers depended on the cell line investigated. The highest efficiencies were observed for polymers whose unfunctionalized PEI cores had molecular weights in the range M(w)=6000-25 000 g mol(-1). The cytotoxicity of the dendrimers generally rises with increasing core size. The data collected for NIH/3T3 and COS-7 cells indicate a maximum transfection efficiency at around 60 % branching for the PPI analogues, and at a PEI-core molecular weight of M(w)=25 000 g mol(-1). PAMAM functionalization of PEI (M(w)=5000 and 21 000 g mol(-1)) leads to polymers with little or no cytotoxity in the cell lines investigated.

Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives

“…An increasing degree of branching is known to increase the in vitro cytotoxic effects, as well as the haemolysis of erythrocytes [22]. Krämer et al synthesized well-defined pseudo dendrimers based on branched PEI and reported the lowest cytotoxicity for a degree of branching of about 60% [23]. Thus, detailed knowledge about the polymer structure is a prerequisite in order to establish clear structure-function relationships, as well as to optimize cytotoxicity and biocompatibility ( Table 6).…”

Self‐Assembly of Hyperbranched Polymers and Its Biomedical Applications

“…[ 184 ] In vitro DNA transfection of polyplexes in several adherent cell lines indicated that the DB of maximum transfection effi ciency was around 0.6. Further increasing DB resulted in signifi cantly low gene transfection effi ciency as a result of the low molecular fl exibility.…”

Kinetic analysis of nanoparticulate polyelectrolyte complex interactions with endothelial cells

“…There are numerous nanoscale constructs, assemblies, architectures, and particulate systems being studied as targeted and drug delivery platforms. These include polymeric micelles, dendrimers, virus-derived capsid nanoparticles (NP), polyplexes, and liposomes [1][2][3][4][5]. These nanovehicles do not behave equivalently; their behavior within the biological microenvironment, stability, extracellular and cellular distribution vary with their chemical makeup, morphology and size [6].…”