Polyplexes biocompatibility

Abstract Carbohydrates have been investigated and developed as delivery vehicles for shuttling nucleic acids into cells. In this review, we present the state of the art in carbohydrate-based polymeric vehicles for nucleic acid delivery, with the focus on the recent successes in preclinical models, both in vitro and in vivo. Polymeric scaffolds based on the natural polysaccharides chitosan, hyaluronan, pullulan, dextran, and schizophyllan each have unique properties and potential for modification, and these results are discussed with the focus on facile synthetic routes and favorable performance in biological systems. Many of these carbohydrates have been used to develop alternative types of biomaterials for nucleic acid delivery to typical polyplexes, and these novel materials are discussed. Also presented are polymeric vehicles that incorporate copolymerized carbohydrates into polymer backbones based on polyethylenimine and polylysine and their effect on transfection and biocompatibility. Unique scaffolds, such as clusters and polymers based on cyclodextrin (CD), are also discussed, with the focus on recent successes in vivo and in the clinic. These results are presented with the emphasis on the role of carbohydrate and charge on transfection. Use of carbohydrates as molecular recognition ligands for cell-type specific dehvery is also briefly... 

Polymethacrylates (PMAs) are acrylic polymers which have a wide range of molecular masses and chemical structures. PMAs can form polyplexes on condensation of polynucleotides on a nanoscale. Although PMAs have only tertiary amine groups, they have been shown to have a similar transfection efficiency potential with a more favorable biocompatibility profile than PEIs. ° ... 

Kanayama N, Fukushima S, Nishiyama N, Itaka K, Jang W-D, Miyata K, Yamasaki Y, Chung U-I, Kataoka K (2006) A PEG-based biocompatible block catiomer with high buffering capacity for the construction of polyplex micelles showing efficient gene transfer toward primary cells. ChemMedChem 1 439-444... 

In addition to natural biopolymers, recent attention has also focused on biocompatible peptides as dehvery vectors. By condensing pDNA in a simple complexation fashion similar to polycations, protein transduction domain peptides demonstrate carrier uptake of 80 to 90% within 30 min, significantly more rapid than PEI or commercial liposomes [28]. These vectors are able to bypass traditional endo-cytic pathways to reach the nucleus within 1 h. Similarly, nuclear localization sequence (NLS) peptides allow superior transfection over synthetic polyplexes, and may be incorporated in traditional liposome complexes to assist in plasmid nuclear penetration [29,30]. 

For clinical use, better defined, homogeneous and biocompatible systems will be necessary. Aspects for optimization will include a defined assembly into monodisperse particle populations preferably of small size [190] methods for the purification of polyplexes [56] which remove potentially... 

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