Synthesis and study of branched hyaluronic acid with potential anticancer activity.

Conjugates of hyaluronic acid (HA) with biologically active molecules showed great potential in many applications. Oligomers of hyaluronic acid (oliHA) as possible regulators of biological processes and potential anti-cancer therapeutics, were reversibly attached via covalent bond on HA modified with an aldehyde group (HA-CHO) using bis-hydrazido or bis-oxyamino spacers. The structure of the final conjugates (HA-spacer-oliHA) was studied by advanced 2-dimensional NMR techniques in detail.

The effect of hydrazide linkers on hyaluronan hydrazone hydrogels.

The effect of hydrazide linkers on the formation and mechanical properties of hyaluronan hydrogels was intensively evaluated. The reaction kinetics of hydrazone formation was monitored by NMR spectroscopy under physiological conditions where polyaldehyde hyaluronan (unsaturated: ΔHA-CHO, saturated: HA-CHO) was reacted with various hydrazides to form hydrogels. Linear (adipic, oxalic dihydrazide) and branched (N,N´,N´´-tris(hexanoylhydrazide-6-yl)phosphoric triamide and 4-arm-PEG hydrazide) hydrazides were compared as crosslinking agents.

Conjugates of modified hyaluronic acid with amino compounds for biomedical applications.

Hyaluronic acid (HA) modified with an aldehyde group (HA-CHO) has enormous potential for the covalent attachment of the amino compounds and for the crosslinking of HA with bis or multi-functional amino linkers under physiological conditions. Modification of HA-CHO to its α,β-unsaturated analogue (ΔHA-CHO) generally increases the stability of the reversible imino-attachment due to conjugation of the imine moiety with the adjacent CC double bound. Conjugation of a wide range of structurally different amines including the amines with enhanced biological activity were studied in detail.

A new unsaturated derivative of hyaluronic acid - Synthesis, analysis and applications.

Hyaluronic acid (HA) containing CC double bond in positions 4 and 5 of N-acetyl-glucosamine ring (ΔHA) is an unique material, which could be used for biomedical applications and cosmetics. The main advantage of the CC double bond is its ability to react with a wide range of oxidation agents. Location of the CC double bond directly on the glucopyranose ring allows to change the chemical capabilities and simultaneously to mimic the intrinsic physical properties of HA without introduction of linkers or other substances.

α,β-Unsaturated aldehyde of hyaluronan--Synthesis, analysis and applications.

Hyaluronic acid (HA) modified with an aldehyde group (HA-CHO or HA-aldehyde) has been extensively used for various biomedical applications. The main advantage of the aldehyde moieties is the ability to react with a wide range of amino compounds under physiological conditions. Reactions of aldehydes with primary amines in water are reversible and equilibrium is thoroughly shifted towards starting aldehyde and amine.