Abstract: Microparticles based on ester derivatives of hyaluronan and related methods and compositions are disclosed. The microparticles comprise a conjugate of all-trans retinoic acid and a particular hyaluronan comprising from 1 to 5000 dimer units; where the microparticles comprise a degree of substitution of all-trans retinoic acid residues in the conjugate of hyaluronan in the range of from 0.1 to 8%. Methods of preparing the microparticles and related compositions are also disclosed.

Abstract: The invention relates to a self-supporting, biodegradable film comprising a C10-C22-acylated derivative of hyaluronic acid according to the general formula (I), where R is H+ or Na+, and where R1 is H or —C(?O)CxHy, where x is an integer within the range from 9 to 21 and y is an integer within the range from 11 to 43 and CxHy is a linear or branched, saturated or unsaturated C9-C21 chain, wherein in at least one repeating unit one or more of R1 is —C(?O)CxHy and where n is within the range from 12 to 4000; a method of preparation thereof and use thereof.

Abstract: The invention relates to an antitumor composition based on hydrophobized hyaluronan and inorganic nanoparticles stabilized by oleic acid. The hydrophobized hyaluronan in the form of an acylated hyaluronan serves in the composition as a carrier of inorganic nanoparticles. Out of the group of inorganic nanoparticles, the composition may comprise superparamagnetic nanoparticles, nanoparticles of ZnO and moreover, upconversion nanoparticles. Said composition is selectively cytotoxic with respect to both suspension and adherent tumor cell lines, especially with respect to tumor cell lines of colorectum carcinoma and adenocarcinoma, lung carcinoma, hepatocellular carcinoma and breast adenocarcinoma. The highest cytotoxic effects were observed in case of the composition based on an oleyl derivative of hyaluronan with SPIONs. The composition of acylated hyaluronan with SPIONs may also be advantageously used for an in vivo detection of accumulation of the composition in the body, preferably in a tumor or in liver.

Abstract: The invention relates to conjugates of hyaluronic acid oligomer according to the general formulae I, II III or IV, or a salt thereof, the method of preparation thereof and use thereof, where the oligomer is bonded to the respective substrate by its ending anomeric center via a bi-functional amino linker by means of an amino or imino bond. This type of conjugates allows releasing oligomers in their native form. The prepared systems exhibited an enhanced biological activity against selected lines of cancer cells.

Abstract: The invention relates to a method of preparation hydrophobized hyaluronic acid (Formula I) and further to a method of encapsulating biologically active substances into the nanomicelles of hydrophobized hyaluronan serving as carriers of biologically active hydrophobic substances. The hydrophobization of hyaluronan is carried out through an esterification reaction of hyaluronan with long-chain carboxylic acids, the latter being activated by a halogenide derivative of 2,4,6-trichlorobenzoic acid or by another organic chloride. In an aqueous environment, water-soluble hydrophobized derivatives can form nanomicelles in which nonpolar substances can be bound by means of non-covalent physical interactions. The core of a nanomicelle is formed by hydrophobic acyl functional groups while the shell of a nanomicelle is formed by hyaluronic acid. The encapsulation of the substances into nanomicelles can be performed by means of the solvent exchange method or by means of sonication.

Abstract: The invention relates to a self-supporting, biodegradable film comprising a C10-C22-acylated derivative of hyaluronic acid according to the general formula (I), where R is H+ or Na+, and where R1 is H or —C(?O)CxHy, where x is an integer within the range from 9 to 21 and y is an integer within the range from 11 to 43 and CxHy is a linear or branched, saturated or unsaturated C9-C21 chain, wherein in at least one repeating unit one or more of R1 is —C(?O)CxHy and where n is within the range from 12 to 4000; a method of preparation thereof and use thereof.

Abstract: The invention relates to an antitumor composition based on hydrophobized hyaluronan and inorganic nanoparticles stabilized by oleic acid. The hydrophobized hyaluronan in the form of an acylated hyaluronan serves in the composition as a carrier of inorganic nanoparticles. Out of the group of inorganic nanoparticles, the composition may comprise superparamagnetic nanoparticles, nanoparticles of ZnO and moreover, upconversion nanoparticles. Said composition is selectively cytotoxic with respect to both suspension and adherent tumor cell lines, especially with respect to tumor cell lines of colorectum carcinoma and adenocarcinoma, lung carcinoma, hepatocellular carcinoma and breast adenocarcinoma. The highest cytotoxic effects were observed in case of the composition based on an oleyl derivative of hyaluronan with SPIONs. The composition of acylated hyaluronan with SPIONs may also be advantageously used for an in vivo detection of accumulation of the composition in the body, preferably in a tumor or in liver.

Abstract: The invention relates to conjugates of hyaluronic acid oligomer according to the general formulae I, II III or IV, or a salt thereof, the method of preparation thereof and use thereof, where the oligomer is bonded to the respective substrate by its ending anomeric center via a bi-functional amino linker by means of an amino or imino bond. This type of conjugates allows releasing oligomers in their native form. The prepared systems exhibited an enhanced biological activity against selected lines of cancer cells.

Abstract: The invention relates to the preparation and use of ?,?-unsaturated aldehyde of hyaluronan having a double bond in the positions 4 and 5 and an aldehydic group in the position 6 of the glucosamine part of the polysaccharide. The method of preparation is based on dehydration of hyaluronan having an aldehydic group in the position 6 of the glucosamine part of the polysaccharide. Two methods have been described, which are dehydration in a solution or heating in solid state in absence of solvents, bases or other additives. This derivative allows stabilization of conjugates of hyaluronan with amino compounds by means of a multiple bond from the aldehyde side, and therefore, it is possible to effectively immobilize practically any compound containing an amino group to such modified hyaluronan in physiological conditions. In case of using a diamine or compounds or polymers containing three or more amino groups, it is possible to prepare crosslinked hyaluronan derivatives.

Abstract: The invention relates to a method of preparation hydrophobized hyaluronic acid (Formula I) and further to a method of encapsulating biologically active substances into the nanomicelles of hydrophobized hyaluronan serving as carriers of biologically active hydrophobic substances. The hydrophobization of hyaluronan is carried out through an esterification reaction of hyaluronan with long-chain carboxylic acids, the latter being activated by a halogenide derivative of 2,4,6-trichlorobenzoic acid or by another organic chloride. In an aqueous environment, water-soluble hydrophobized derivatives can form nanomicelles in which nonpolar substances can be bound by means of non-covalent physical interactions. The core of a nanomicelle is formed by hydrophobic acyl functional groups while the shell of a nanomicelle is formed by hyaluronic acid. The encapsulation of the substances into nanomicelles can be performed by means of the solvent exchange method or by means of sonication.

Abstract: The invention relates to the preparation and use of ?,?-unsaturated aldehyde of hyaluronan having a double bond in the positions 4 and 5 and an aldehydic group in the position 6 of the glucosamine part of the polysaccharide. The method of preparation is based on dehydration of hyaluronan having an aldehydic group in the position 6 of the glucosamine part of the polysaccharide. Two methods have been described, which are dehydration in a solution or heating in solid state in absence of solvents, bases or other additives. This derivative allows stabilization of conjugates of hyaluronan with amino compounds by means of a multiple bond from the aldehyde side, and therefore, it is possible to effectively immobilize practically any compound containing an amino group to such modified hyaluronan in physiological conditions. In case of using a diamine or compounds or polymers containing three or more amino groups, it is possible to prepare crosslinked hyaluronan derivatives.