Polymeric hyaluronan

In addition, the tetramers are seen to interact to form long chains (beaded filaments). Dimers, tetramers, and polymeric chains all have 30-75-30 nm spacing between the globular ends (Furthmayr et al., 1983 Von Der Mark et al., 1984 Wu et al., 1987). Collagen VI is found to bind to hyaluronan (Kielty et al., 1992), biglycan and decorin (Wiberg et al., 2001), fibrillin (Ueda and Yue, 2003), and other matrix constituents. 

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... 

Yun YH, Chen W (2005) Microspheres formulated from native hyaluronan for applications in gene therapy. In Mansoor MA (ed) Polymeric gene delivery principles and applications, CRC Press LLC, USA, pp 475 186... 

Kobayashi S, Morii H, Itoh R, Kimura S, Ohmae M. Enzymatic polymerization to artificial hyaluronan a novel method to synthesize a glycosaminoglycan using a transition state analogue monomer. J. Am. Chem. Soc. 2001 123 11825-11826. 

Hyaluronan is the most common negatively charged glycosaminoglycan in the human vitreous humor, and is known to interact with polymeric and liposomal DNA complexes, where hyaluronan solutions have been shown to decrease the cellular uptake of complexes.This is useful for enhancing the availability and retention time of drugs administered to the eye. It is immunoneutral, which makes it useful for the attachment of biomaterials for use in tissue engineering and drug delivery... 

Figure 9.15 Enzymatic polymerization of various monomers (series 1) to synthetic hyaluronan and its derivatives (series 2). (Reproduced with permission from [231]. Copyright (2005) American Chemical Society).

Polymerization of the 3-l,4-glucan chain is catalyzed by cellulose synthase enzymes. All known cellulose synthases are family 2 processive glycosyltrans-ferases, a ubiquitous family of enzymes which also includes chitin synthases, hyaluronan synthases, and NodC proteins (Saxena et al. 2001). Cellulose synthase sequences share a highly conserved catalytic region containing the D, D, D,... 

Another class of polymers where hydrolases are used successfully comprises polysaccharides. This approach has been pioneered by Kobayashi et al (3c,36) and is exemplified by their article (18) where hyaluronan and chondroitin were prepared via hyaluronidase-catalyzed polymerizations. A slightly different approach is to use glycosidases to prepare oligosaccharides (17,37). 

During lyophilization of hyaluronan solutions, polysaccharide degradation is initiated with phosphate ions [50]. For purification from proteins, proteolitic enzymes could also be used to reduce the viscosity of the biopolymer, particularly papain SH-groups that are reducing agents and accelerate the decomposition of hyaluronan [34], Trypsin, which contains Fe " ions, could also be used for the purification of hyaluronan and to initiate the depolymerization process. The use of 8-hydroxyquinoline prevents HA viscosity reduction [25]. In order to maintain the polymerization level of hyaluronan, the initial tissue must be thoroughly washed from blood, which contains ions of iron, copper and phosphate. 

Almond, A., Brass, A., Sheehan, J.K. (1998) Deducing polymeric structure from aqueous molecular dynamic simulations of oligosaccharides prediction from simulation of hyaluronan tetrasaccharides compared with hydrodynamic and X-ray fiber diffiaction date. Journal of Molecular Biology, 1425-143. 

In the next section, the properties of hyaluronan microimplants are discussed from the contemporary viewpoint of physical chemistry of gel-like polymeric materials. 

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