FR2967580A1 - Material, useful to prepare composition e.g. food composition, comprises an acidic polysaccharide comprising poly(galacturonate), heparin, hyaluronic acid, chondroitin sulfate, pectin or neutral polysaccharides such as cellulose or dextran - Google Patents

Abstract

Material comprises at least one acidic polysaccharide comprising poly(galacturonate), heparin and its derivatives, hyaluronic acid and its derivatives, chondroitin sulfate, pectin and its derivatives, or neutral polysaccharides such as cellulose or dextran and their derivatives, modified by carboxylate and/or sulfate groups, including a hydrophobic moiety that has a molar content of at least 2% over the repeat units, and at least one biopolymer comprising cationic polyamino acids or polysaccharides bearing cationic groups comprising mono-, di-, tri-alkylamino or tetraalkylammonium. Material comprises at least one acidic polysaccharide comprising poly(galacturonate), heparin and its derivatives, hyaluronic acid and its derivatives, chondroitin sulfate, pectin and its derivatives, or neutral polysaccharides such as cellulose or dextran and their derivatives, modified by carboxylate and/or sulfate groups, including a hydrophobic moiety that has a molar content of at least 2% over the unit of repetition, and at least one biopolymer comprising cationic polyamino acids or polysaccharides bearing cationic groups comprising mono-, di-, tri-alkylamino or tetraalkylammonium, where the biopolymer comprises a cationic molar content of cationic group of at least 25% over the repeat units, and optionally at least one active substance, preferably hydrophobic substance. Independent claims are included for: (1) preparing the material, comprising depositing layer-by-layer, preferably by alternating layers, of acidic polysaccharide and cationic biopolymer; and (2) a device, preferably medical implant or implantable biomaterial, comprising the material.

Description

MATERIAL COMPRISING AN ACIDIC POLYSACCHARIDE AND A CATIONIC BIOPOLYMER

The present invention relates to a material formed of bio-polyelectrolytes, in particular acidic polysaccharide and cationic biopolymer, in particular used for the solubilization and the transport of active substances which are poorly soluble in water.

The delivery of active ingredients to an organ, tissue or cells is a major concern today. Problems encountered for effective delivery include solubility, stability, pharmacokinetics, bio-distribution of said active ingredients, as well as unsatisfactory targeting. The effectiveness of disease treatments, for example of infectious or cancerous diseases, can be improved by specific delivery. In the particular case of hydrophobic active ingredients (PA), one of the problems is their low solubility in water which makes it difficult or impossible to obtain satisfactory delivery. One of the solutions to overcome all or part of this delivery problem is the vectorization of these active principles. This vectorization therefore aims to improve the solubility, stability, pharmacokinetics and / or bio-distribution of said active principles, and / or their specific targeting. Vectorization systems have already been described in the literature. They may especially be in the form of micelles, micro / nanospheres, micro / nanocapsules, lipid or polymeric vesicles. Polymer micelles can be characterized by their core-shell structure in equilibrium with the amphiphilic molecules in solution. Micelles have been described in the literature, in particular by Jones et al., (Eur J. Biopharm, 1999, 48, 101), by Torchilin (Pharm Res., 2007, 24, 1), or in the WO application. 99/61512. These micelles may exhibit storage and / or post-injection stability which limits their use as PA vectors. The micro / nanospheres may be formed by a biodegradable polymer matrix such as poly (lactide) / poly (lactide-co-glycolide) of the polyester family. These systems can be synthesized by numerous methods, the most common of which are solvent emulsion-evaporation, "salting-out", nanoprecipitation and emulsion-diffusion, for example described by Soppimath et al. (J. Control Release, 2010, 70, 1). These methods are generally effective for encapsulating hydrophobic active ingredients with high yields. However, they require the use of organic solvents. On the other hand, the release being controlled by diffusion / erosion phenomena, this can lead to peaks of release ("burst effect") observed in particular with the poly (lactide) / poly (lactide-co-glycolide) particles. and whose control is random (Huynh et al., Int J Pharm, 2009, 379, 2010, Shah et al., Pharm Res, 2006, 23, 2638).

It has also been described hydrophobicized biopolymers by grafting lipophilic groups derived from alcohol or cholesterol precursors (Akiyoshi et al., J. Control Release, 1998, 54, 313, Park et al., J. Control Release, 2009, 135 , 259, Hwang et al., J. Control Release, 2008, 128, 23, Nam et al., J. Control Release, 2009, 135, 259, FR 2 855 521). These can lead to the formation of matrix nanoparticles.

However, they may exhibit variable stability after incorporation of the hydrophobic active ingredient (Saravanakumar et al., J. Control Release, 2009, 140, 210). Liposome vectorization systems (lipid vesicles) and polymer vesicles are studied intensively. Several anti-cancer agent formulations are currently in the clinical phase, some of which have been approved for clinical use (Haley et al., Urol, Oncol., 2008, 26, 57). These assemblages are in general non-toxic and biocompatible. However, they frequently have limitations in terms of encapsulation capacity, stability and production, as well as early release of hydrophilic active agents into the blood (Alphandary et al., Int. J. Antimicrob Agents, 2000, 13, 155).

A vectorization system consisting of lipid nanocapsules capable of incorporating hydrophobic active ingredients has been proposed in application WO 2001/064328. These nanocapsules have the advantage of being formulated in the absence of organic solvents, unlike the systems described above, however they contain surfactants constituting the hydrophilic wall and coating the oily heart with triglycerides.

Furthermore, a solution to avoid the use of surfactants has been developed in the application WO 1998/014180 and consists in using polyelectrolytes as a solubilizing agent for hydrophobic active ingredients. This method makes it possible to prepare aqueous colloidal dispersions of hydrophobic active molecules. This approach was then extended to the synthesis of hydrophobic PA nanoparticles using the layer-by-layer deposition technique to coat aggregates (called crystals) of hydrophobic active ingredients (Agarwal et al., J. Control Release, 2008). Chen, et al., Nanomedicine, 2009, 5, 316). However, this process may have insufficient control of the size of the particles, these depending on the size of the active ingredient crystals. Thus, the vectorization systems described in the prior art may have drawbacks in terms of ease and / or cost of preparation, amount of vectorized active ingredients, biocompatibility, in particular vector metabolism, stability, in particular in a physiological medium, for delivery of the incorporated substance, control of the encapsulation rate and / or salting out (in particular in order to completely or partially avoid a "burst" effect), pharmacokinetics, bio-distribution of said active ingredients A, targeting, versatility of use and / or adaptability with respect to different active principles, biocompatibility with the organism and / or with the active principle, size and / or shape of the vector, especially film or capsule.

The present invention therefore aims to solve the problems mentioned above in whole or in part. According to a first aspect, the subject of the invention is a material comprising, or even consisting of: at least one acid polysaccharide chosen from poly (galacturonate) s, heparin and its derivatives, hyaluronic acid and its derivatives, chondroitin sulphates, pectin and its derivatives, neutral polysaccharides, such as cellulose or dextran and their derivatives, modified with carboxylate and / or sulphate groups, some of whose repeating units carry a hydrophobic unit at a molar content of at least 2% relative to the repeating unit; at least one cationic biopolymer chosen from polyamino acids and polysaccharides bearing cationic groups, chosen from mono-, di-, tri-alkylamino or tetraalkylammonium groups, this cationic biopolymer; comprising a molar content of cationic group of at least 25% with respect to the repeating unit, and optionally at least one active substance, notam hydrophobic.

In particular, said material is formed, at least in part, by the pairing of biopolymers of opposite charges, for example acid polysaccharide and cationic biopolymer. For example, the acid polysaccharide comprises negative charges and the cationic biopolymer comprises positive charges that develop charge interactions. These biopolymers of opposite charges can be obtained by the layer-by-layer deposition technique, especially as described by O. Decher et al., Thin Sa / ID Films 1992, 0 831, or by Y. Lvov, et al. , Physica B 1994, 198, 89. For the purposes of the present invention, the term "biopolymer" means a biocompatible polymer capable of being metabolized by the organism into biocompatible metabolites, in particular the biopolymer is chosen from polysaccharides and polyamino acids . By "derivative" is meant in the sense of the present invention a compound which is deduced from another by a simple addition or a substitution. In the present case, a polysaccharide derived from a polysaccharide may have hydroxyl functions substituted or modified in other functions. For example, hydroxyl functions may be converted into ester or amide functions, or hydroxyl functions may be protected, in particular by protective groups, in particular as defined in Green's Protective Groups in Organic Synthesis 4th ed.

In particular, a derivative comprises less than 20% by number of modified functions. For the purposes of the present invention, the term "active substance" is intended to mean a compound or a combination of compounds, optionally in the form of salt (s), providing the activity or part of the activity of the composition comprising them.

Such an active substance may be: - a pharmacological or phytosanitary active substance, - a cosmetic active substance, in particular a dermatological substance, and - a medicinal active substance. A pharmacological active substance, may be a molecule which is or has been the subject of a marketing authorization in a country, in particular a country chosen from among the countries constituting the European Union, Switzerland, the United States , Japan, China, India and Brazil.

A cosmetic active substance may be a compound having the cosmetic activity in the cosmetic composition. An active substance of the food type may be a compound having the food activity in the foodstuff.

For the purposes of the present invention, the term "hydrophobic active substance" means an active substance, optionally in the form of a salt, having a solubility in water at 25 ° C. of less than or equal to 200 μg / l, in particular less than or equal to at 150 μg / 1, even less than or equal to 100 μg / 1, and most preferably less than or equal to 50 μg / 1. The materials obtained, in particular films and capsules, can result from the complexation of polyanion (s), such as the acidic polysaccharide, with at least one polycation, such as the cationic biopolymer. This complexation can be the very principle of the formation of these materials. The acidic polysaccharide may comprise one or more, including two or three, types of osidic units per repeating unit. In particular, the repeating unit comprises two types of osidic units, in particular D-glucuronic acid and N-acetyl-D-glucosamine. The acid polysaccharide is chosen from poly (galacturonate) s, heparin and its derivatives, hyaluronic acid and its derivatives, chondroitin sulphates, pectin and its derivatives, neutral polysaccharides such as cellulose, dextran and their derivatives. derivatives, modified with carboxylate groups and / or sulphates. The carboxylate or sulphate groups of the neutral polysaccharides can be inserted via the grafting of a carboxymethyl group, or by sulphonation using a SO3-amine complex, such as SO3-ME3N (trimethylamine) or SO3-Et3N. (triethylamine), SO3-Pyridine, and SO3-Piperidine or non-amino complex type such as SO3-DMF. Thus, among the derivatives of cellulose or of dextran, there may be mentioned carboxymethylcellulose, dextran sulfate, or carboxymethyl-dextran sulfate. In particular, the acid polysaccharide comprises at least 100, in particular at least 200, in particular at least 300, or even at least 400 repeating units. The hydrophobic unit may be grafted onto a carboxylic acid function, an alcohol function of the acidic polysaccharide.

According to a particular embodiment, the hydrophobic unit is grafted on a carboxylic acid function of the acidic polysaccharide. When the hydrophobic unit is grafted onto an alcohol function of the acid polysaccharide, it can be grafted via an ester or ether function.

When the hydrophobic unit is grafted on a carboxylic acid function, it may be grafted via an amide, ester or -CONHNHCO- function, called "carbonylhydrazide". In particular, the hydrophobic unit is grafted onto a carboxylic acid function via a carbonylhydrazide. The hydrophobic unit may be a hydrocarbon unit comprising at least six carbon atoms. It may optionally comprise, in addition to the binding with the acidic polysaccharide, at least one functional group chosen from alcohols, thiols, ethers, thioethers, esters, thioesters, amides, carbamates, aldehydes, ketones, ketals, acetals, nitro, nitriles, imines, oximes, hydrazides and carbonylhydrazides. In particular, it comprises at most three, in particular two functions as defined above, or even a function as defined above. The hydrophobic unit may especially comprise at least one selected from thioethers, esters, thioesters, amides, carbamates, aldehydes, ketones, ketals, acetals, nitro, nitriles, imines, oximes, hydrazides and carbonylhydrazides. According to a variant it comprises one, two or three functions as defined above, particularly it comprises one or two, or it includes one. According to a particular embodiment, the hydrophobic unit is bonded to the acid polysaccharide via a carbonylhydrazide bond and comprises 0 or 1 carbonylhydazyde function, in particular to the exclusion of any other function.

Furthermore, the hydrophobic unit may comprise saturated or unsaturated, linear, branched and / or cyclic aliphatic chains, and aryl groups, such as benzyls, tolyls, phenyls or naphthyls, or even heteroaryls, such as pyridynyls. In particular, the hydrophobic unit can be grafted onto a carboxylic acid function by forming a carbonylhydrazide (-CONHNHCO-) type bond. In this case, the unit may be of the type -CONHNHCORI (CONHNH) mR2 where R1 represents an alkylene or a polyether, such as poly (ethylene glycol), comprising from 1 to 17 carbon atoms, an alkenyl or an alkynyl comprising from 2 to 17 carbon atoms, an aryl comprising from 6 to 17 carbon atoms, these groups possibly comprising at least one functional group chosen from alcohols, thiols, ethers, thioethers, esters, thioesters and amides; carbamates, aldehydes, ketones, ketals, acetals, nitro, nitriles, imines, oximes, hydrazides and carbonylhydrazides, om representing 0 or 1, where Rz is H, alkyl or polyether comprising from 6 to 17 carbon atoms, an alkenyl or an alkynyl comprising from 6 to 17 carbon atoms, an aryl or an arylalkyl comprising from 6 to 17 carbon atoms, these groups possibly comprising at least one function selected from the group consisting of alcohols, th iols, ethers, thioethers, esters, thioesters, amides, carbamates, aldehydes, ketones, ketals, acetals, nitro, nitriles, imines, oximes, hydrazides and carbonylhydrazides. The alkyls, alkylenes, polyethers, alkenyls and alkynyls may be linear, branched or cyclic. They may also be substituted for example by halogen atoms, such as chlorine or fluorine, or by aryls. The aryls can be substituted, for example by halogen atoms, such as chlorine or fluorine, or alternatively by alkyls. In particular, the hydrophobic unit is of the CONHNHCORI (CONHNH) mR2 type with R1 represents an alkylene or a polyether comprising from 1 to 17 carbon atoms, devoid of other chemical functions or with at least one function chosen from among the ethers, thioethers, esters, thioesters, amides, carbamates, aldehydes, ketones, ketals, acetals, nitriles, imines, oximes and hydrazides, in particular the alkylene group is of the type - ( CH 2) X with x representing an integer ranging from 1 to 17, in particular from 2 to 10, even from 3 to 8, and in particular of 4, and the polyether is a polyethylene glycol or a polypropylene glycol, om representing 0 or 1 in particular m is 1, where Rz is H, an alkyl or polyether comprising 6 to 17 carbon atoms, has no other chemical functions or at least one function selected from ethers, thioethers, esters, the th ioesters, amides, carbamates, aldehydes, ketones, ketals, acetals, nitriles, imines, oximes and hydrazides, in particular the alkylene group is of the - (CH2) y-CH3 type with y representing an integer ranging from 6 to 16, in particular from 7 to 14, or even from 8 to 11, and in particular from 9. According to one particular embodiment, the hydrophobic unit is of the type - CONHNHCORI (CONHNH) mR2 where o RI represents - (CH2) X with x representing an integer ranging from 1 to 17, in particular from 2 to 10, even from 3 to 8, and in particular from 4, om represents 1, where Rz representing H or an alkylene group of type - (CH2) y-CH3 with y being an integer ranging from 6 to 16, in particular from 7 to 14, or even 8 to 14, and in particular of 9. The molar grafting rate of the hydrophobic unit may range from 5 to 40%, especially 10 to 30%, or even about 20% relative to the repeat unit. The substituted polysaccharide may represent from 10% to 90% by weight relative to the total weight of the material.

According to a particular embodiment, the polysaccharide comprises, or even consists of, hyaluronic acid, in particular of formula (I): OH Formula (I) in which - n is an integer ranging from 250 to 2500, in particular from 450 to 1500, and - R represents - OH, - OZ, with Z being a monovalent counter ion such as Na + or K + or a divalent counterion, such as Cal + or Mg2 +, in particular Z is a monovalent ion, 25 - NHNHCORI ( Where R 1 represents an alkylene or a polyether comprising from 1 to 17 carbon atoms, an alkenyl or an alkynyl comprising from 2 to 17 carbon atoms, an aryl comprising from 6 to 17 carbon atoms, these groups being able to comprise or not at least one function selected from alcohols, thiols, ethers, thioethers, esters, thioesters, amides, carbamates, aldehydes, ketones, ketals, acetals, nitro, nitriles, imines, oximes, hydrazides and carbonylhydrazides , om represents 0 or 1, where Rz represents H, an alkyl or a polyether comprising from 6 to 17 carbon atoms, an alkenyl or an alkynyl comprising from 6 to 17 carbon atoms, an aryl or an arylalkyl comprising from 6 to 17; carbon atoms, these groups possibly comprising at least one functional group chosen from alcohols, thiols, ethers, thioethers, esters, thioesters, amides, carbamates, aldehydes, ketones, ketals, acetals, nitro, nitriles, imines, oximes, hydrazides and carbonylhydrazides, with a molar grafting rate of the hydrophobic unit greater than or equal to 2%, in particular the degree of grafting can range from 5 to 40%, in particular from 10 to 30%, or even about 20% with respect to the repeat unit. In particular, the hydrophobic unit is of the type - CONHNHCORI (CONHNH) mRz with RI represents an alkylene or a polyether comprising from 1 to 17 carbon atoms, devoid of other chemical functions or with at least one function chosen from ethers, thioethers, esters, thioesters, amides, carbamates, aldehydes, ketones, ketals, acetals, nitriles, imines, oximes and hydrazides, in particular the alkylene group is of the - (CH 2) type X, and the polyether group is of the type - (CH2CHCH3O) r or - (CH2CH2O) s, o with x, representing an integer ranging from 1 to 17, in particular from 2 to 10, or even from 3 to 8, and 4, r representing an integer ranging from 1 to 5, in particular from 1 to 4, or even from 1 to 3, and s representing an integer ranging from 1 to 8, in particular from 2 to 5, or even 3 at 6, where om is 0 or 1, in particular m is 1, where Rz is H or alkyl is comprising from 6 to 17 carbon atoms, devoid of other chemical functions or with at least one function selected from ethers, thioethers, esters, thioesters, amides, carbamates, aldehydes, ketones, ketals, the acetals, nitriles, imines, oximes and hydrazides, in particular the alkylene group, is of the - (CH 2) y -CH 3 type with y representing an integer ranging from 6 to 16, in particular from 7 to 14, and even from 8 to 11, and in particular of 9. According to a particular embodiment, the hydrophobic unit is of the type - CONHNHCORI (CONHNH) mR2 where o RI represents - (CH2) X with x representing an integer ranging from 1 to 17 , in particular from 2 to 10, even from 3 to 8, and in particular from 4, om represents 1, where Rz represents H or an alkylene group of the - (CH2) y-CH3 type with y representing an integer ranging from 6 to at 16, in particular from 7 to 14, or even from 8 to 11, and in particular from 9. Hyaluronic acid g reffered can represent from 10% to 90% by weight relative to the total weight of the material. The acidic polysaccharides grafted with hydrophobic units, and more particularly the hyaluronic acids of Formula (I) can be obtained by means of the protocols described in WO 2007/059890 or in Biomacromolecules, 2009, 10, 2875-2884. The cationic biopolymer is chosen from polyamino acids and polysaccharides bearing cationic groups, mono-, di-, tri-alkylamino or tetraalkylammonium, comprising a molar content of amino group or tetraalkylammonium of at least 25%. By "cationic biopolymer" is meant, for example, a biopolymer having a molar content of positive charges of at least 25% per repeating unit. This cationic biopolymer may comprise one or more, in particular two or three, units of amino acid or osidic residue type, per repeating unit.

The cationic group, mono-, di-, tri-alkylamino or tetraalkylammonium, can be present directly on the biopolymer, this is for example the case of poly (L-lysine), and / or be grafted onto the biopolymer. When the cationic group, especially when it is tetraalkylammonium, grafted, it can be via an ether or amine function, particularly secondary. In particular, the grafting can be carried out by opening an epoxide type ring with an alcohol or amine function, in particular a primary function, with the biopolymer.

Thus, the cationic group may be grafted via the opening of an epoxide of Formula A according to formula A in which - Ra, Rb, Rc, which may be identical or different, represent H or an alkyl comprising from 1 to 6 carbon atoms, and in particular Ra, Rb, Rc, which may be identical or different, represent an alkyl comprising from 1 to 6 carbon atoms, m 'is an integer ranging from 1 to 6, in particular from 1 to 4, or even is 1 or 2. - In particular, Ra, Rb and Rc are identical and represent an alkyl comprising from 1 to 6 carbon atoms, in particular methyl, ethyl, propyl or butyl. In particular, the grafting can be carried out via a glycidyl tetraalkylammonium, especially tetramethylammonium, in acidic or neutral medium as described by Cho et al., Biomacromolecules, 2006, 7, 2845, by Seong et al., J. Appl. Polym. Sci., 2000, 76, 2009 or Lim et al., Carbohydr. Res., 2004, 339, 313. The biopolymer can have a molar grafting rate of at least 35%, especially at least 50% relative to the number of repeating units. More particularly, the molar grafting rate may range from 25 to 300%, especially from 35 to 200%, or even from 50 to 150%, with respect to the repeating unit. The cationic biopolymer may represent from 10 to 90% by weight relative to the total weight of the material. In particular, the weight ratio acidic polysaccharide / cationic biopolymer ranges from 10/1 to 1/10.

According to a first variant, the cationic biopolymer is a cationic polysaccharide, in particular the cationic biopolymer comprises, or even consists of, chitosan carrying a cationic group. In particular, the cationic biopolymer may correspond to the chitosan of Formula (II) below: ## STR2 ## in which - n 'is an integer ranging from 150 to 3,000, in particular from 200 to 2,550, and in particular from 200 to 2,000, R'1 and R'z represent, independently of one another, H, or -R'4NR'aR'bR'c, with - R'4 representing a spacer of the type - (CH2) x, - or -CHOH (CH2) X, - and x 'representing an integer ranging from 1 to 6, in particular representing 1 or 2, - R'a, R'b, R'c, identical or different, representing H or an alkyl comprising from 1 to 6 carbon atoms, and in particular R'a, R'b, R'c, identical or different, represent an alkyl comprising from 1 to 6 carbon atoms, or even R'a, R b, R'c, which may be identical or different, represent an alkyl comprising from 1 to 4 carbon atoms, and in particular methyl, ethyl, propyl or butyl, R'3 represents H, an acetyl group or -R "SNR" aR "bR" c, with - R "5 representing u n spacer of the type - (CH 2) X - or --CHOH (CH 2) X - and x - represents an integer ranging from 1 to 6, in particular representing 1 or 2, - R "a, R" b , R "c, identical or different, representing H or an alkyl comprising 1 to 6 carbon atoms, and in particular R" a, R "b, R" c, identical or different, represent an alkyl comprising from 1 to 6 carbon atoms, or R "a, R" b, R "c, identical or different, represent an alkyl comprising from 1 to 4 carbon atoms, and in particular methyl, ethyl, propyl or butyl, in particularly with a graft molar content of at least 25% with respect to the repeating unit. In particular, the molar grafting rate can range from 25 to 250%, or even from 30 to 150%, with respect to the repeating unit. According to a particular embodiment, the chitosan is grafted, in particular as defined above. It may especially be grafted by reacting an alcohol or an amine with a reactive group such as an epoxide group, or with a leaving group such as a halide or a tosylate, with a compound bearing a cationic function, such as an ammonium quaternary. For example glycidyl trimethylammonium chloride in an aqueous medium, at acidic or neutral pH as described by Cho et al., Biomacromolecules, 2006, 7, 2845, by Seong et al., J. Appl. Polym. Sci., 2000, 76, 2009 and Lim et al., Carbohydr. Res., 2004, 339, 313. According to one variant, the chitosan may correspond to Formula (II) in which R '1 and R' 2 represent H and R '3 represents H, an acetyl group or -R "SNR" aR "bR" c, with - R "5 representing a spacer of the type (CH2) x, or CHOH (CH2) X" and x "representing an integer ranging from 1 to 6, in particular representing 1 or 2, - R "a, R" b, R "c, identical or different, representing H or an alkyl comprising 1 to 6 carbon atoms, and in particular R" a, R "b, R" c, identical or different, represent an alkyl comprising from 1 to 6 carbon atoms, or even R "a, R" b, R "c, identical or different, represent an alkyl comprising from 1 to 4 carbon atoms, and in particular methyl, ethyl , propyl or butyl, and the molar grafting rate can range from 25 to 250%, or even from 30 to 150% relative to the number of repeating units.In another variant, chitosan can meet the formula ( II) with a grafting of the groupem cationic acid on the hydroxyls and / or amines, in particular with a molar grafting rate which ranges from 25 to 250%, or even from 30 to 150%, with respect to the repeating unit. When the material comprises as cationic biopolymer cationic polysaccharide, such as chitosan carrying one or more types of cationic group (s), said material may be free of crosslinking between the acidic polysaccharide and the cationic polysaccharide. According to a second variant, the cationic biopolymer is a polyamino acid, in particular the biopolymer comprises, or even consists of, poly (L-lysine). When the material comprises as cationic biopolymer of the polyamino acid, said material may have a crosslinking between the acid polysaccharide and the cationic polyamino acid, the crosslinking may in particular be carried out via a peptide-type bond. This can especially be done in the case where the material is in the form of film or capsules, in particular capsules. According to a still more particular embodiment, the material comprises, or even consists of: - hyaluronic acid of Formula (I) as defined above, - chitosan of Formula (II) as defined above, and optionally an active substance. According to a still more particular embodiment, the material comprises, or even consists of: - hyaluronic acid of Formula (I) as defined above, - poly (L-Lysine) or PLL, - and optionally an active substance. In particular, this material has a crosslinking between the poly- (L-lysine) and the polysaccharide, in particular of the peptide bonding type between the amine functions of the PLL and the acid functions of the polysaccharide. Such crosslinking can be carried out as described in the article by Szarpak et al., Biomacromolecules, 2010, 11, 713. The pharmaceutical active substances that can be used can be chosen from anti-virals, anti-cancer agents, antibiotics, anti-mycotic, adjuvants for vaccines. In particular, the active substances used are hydrophobic. Among the active substances one can particularly mention paclitaxel and saquinavir. The material comprising an acid polysaccharide and a cationic biopolymer may be obtained by layer-by-layer deposition, and in particular by alternating layers of acidic polysaccharide and cationic biopolymer. The formation of this material results from the formation of polyanion / polycation complexes. It can in particular be obtained by the protocols described by G. Decher et al., Thin Sol, 1992, 210, 831, or by Y, Lvov, et al., Phys, 1994, 198, 89.

Thus, the present invention also relates to a method for preparing a material according to the invention comprising layer-by-layer deposition steps, and in particular alternating layers of acidic polysaccharide and cationic biopolymer. Of course, the material may comprise polysaccharides and / or cationic biopolymers of different types, either within the same layer, or in different layers, or both. In particular, especially prior to the manufacture of the material, and in particular layer-by-layer deposition, the active substance is complexed with the grafted acidic polysaccharide as defined above and / or with the cationic biopolymer.

In particular, a hydrophobic active ingredient may be complexed with an acidic graft polysaccharide as defined above. In the case of a non-hydrophobic active ingredient, the latter may be complexed with a cationic biopolymer as defined above or with an acid polysaccharide.

Furthermore, the material can be obtained in capsule form, for example by coating a colloidal biodegradable particle, such as CaCO3, with the multilayer film described above and then dissolving the particle, for example with a chelant, such as EDTA, ethylene diamine tetraacetic acid. The material may be in the form of a film deposited on a solid support or capsules, in particular microcapsules. These capsules or microcapsules can be hollow. In the case of capsules, the material may comprise a number of pairs of layers ranging from 3 to 30, in particular from 3.5 to 20, in particular from 4 to 15, or even from 4.5 to 12. In the case of films the material may comprise a number of pairs of layers ranging from 3 to 100, in particular from 4 to 50, in particular from 5 to 25, even from 5 to 15, and especially from 5 to 10. The present invention further relates to a composition, in particular a cosmetic, pharmaceutical or food composition, for example of the food-grade type, comprising a material as defined above. In particular, the composition is formulated to allow oral, nasal, parenteral administration. The present invention according to another of its aspects also relates to a device, in particular of implantable biomaterial type or medical implant, such as a stent, comprising a material as defined above. According to another of its aspects, the present invention relates to a surface coated in whole or in part, in particular via covalent bonds, with a material as defined above.

Examples In the present examples the following abbreviations are used: HA corresponds to hyaluronic acid and more particularly HA1 OC10 corresponds to a hyaluronic acid (HA) whose carboxylic acid function is grafted with NHNHCO (CH2) 4CONHNH ( CH2) 9CH3 with a molar grafting rate of 10%; it is prepared from a batch of initial hyaluronic acid obtained by bacterial fermentation and having an average molecular weight MW = 200,000 g / mol, - HA20C10 corresponds to a hyaluronic acid whose carboxylic acid function is grafted with NHNHCO (CH 2) 4CONHNH (CH2) 9CH3 with a molar grafting level of 20%, - QCHI corresponds to chitosan grafted with -CH2CHOHCHN + (CH3) 3.C1- and obtained from a batch of initial chitosan (from FMC BioPolymer AS, Novamatrix, Norway), having a N-acetylation degree of 9% and an average molecular weight MW of 372000 g / mol. More specifically, QCHI corresponds to: - QCHI-1 having a grafting only on the amine function of chitosan and a molar grafting rate of 31%, - QCHI-2 having a grafting only on the amine function of chitosan and a grafting rate 66% molar, - QCHI-3 having a grafting on the amine and alcohol functions of chitosan and a molar grafting rate of 93%, - QCHI-4 having a grafting on the amine and alcohol functions of chitosan and a grafting rate molar of 111% and - QCHI-5 having a grafting on the amine and alcohols functions of chitosan and a molar grafting rate of 133%, - PLL corresponds to poly (L-lysine hydrobromide) from SIGMA of mass Mw (15000 -30000) g / mol in the case of capsules and mass Mw - 70000 g / mol in the case of flat films. Furthermore, HAlOC10 and HA20C10 can be obtained using the protocol described in WO 2007/059890 or in Biomacromolecules, 2009, 10, 2875-2884 and QCHI-1, QCHI-2, QCHI-3 and QCHI-4 can be obtained by using the protocol described by Seong et al., J. Appl. Polym. Sci., 2000, 76, 2009, Cho et al., Biomacromolecules, 2006, 7, 2845, or Lim et al., Carbohydr. Res., 2004, 339, 313.

EXAMPLE 1 Preparation of hydrophobic grafted / PLL or QCHI HA films The polyelectrolyte solutions were prepared in PBS buffer (phosphate buffered saline pH 7.4) at a concentration of: 2 g / L for the hydrophobic grafted HA ( HA20C10 or HAlOC10), - 0.5 g / L for PLL and - 2 g / L for QCHI (QCHI-1, QCHI-2, QCHI-3, QCHI-4 or QCHI-5) A precursor layer of poly (Ethylenimine) (5 mg / mL) is deposited to increase the adhesion of the film to the bottom of the well, then the polyelectrolyte solutions (50 μL) are deposited successively in each well. After 8 minutes of adsorption, the wells are rinsed twice for 1 min using the PBS buffer. The sequence is repeated until a film comprising 8 pairs of layers is obtained (acidic polysaccharide / cationic biopolymer) g. For the cross-linking experiments of the water-soluble carbodiimide films, 1-ethyl-3- (3-dimethylamino-propyl) carbodiimide (EDC, 200 mM) was introduced in contact with the films in the presence of N-hydrosulfosuccinimide (50 mM). . This reaction, which is carried out in a medium containing 0.15 M NaCl adjusted to pH 5.5, consists of reacting the ammonium groups of the PLL with the carboxylic groups of the hydrophobic grafted HA to form covalent bonds of amide type (Richert Biomacromolecules 5, 284-294, 2004). The crosslinking agent solution is brought into contact with the film overnight at 4 ° C. Then the films are rinsed for 1 hour with PBS buffer in order to stop the crosslinking and eliminate the soluble products of the reaction. The following films comprising 1, 2, 3, 4, 5, 6, 7, 8 pairs of layers were synthesized according to the protocol described above: HAlOC10 / QCHI-2; HAlOC10 / QCHI-3; HAlOC10 / QCHI-4; HAlOC10 / QCHI-5; HA20C10 / QCHI-2; HA20C10 / QCHI-3; HA20C10 / QCHI-4; HA20C10 / QCHI-5; HAlOC10 / PLL and HA20C10 / PLL. Growth of films (hydrophobic grafted PLL / HA) and hydrophobic grafted QCHI / HA were followed by infrared spectroscopy and UV spectroscopy.

In particular, FIG. 1 represents the growth of the films (PLL / HA20C10) and (QCHI-4 / HA20C10) followed: (A) by absorbance spectroscopy at 230 nm, and (B) by infrared spectroscopy in total internal reflection mode which makes it possible to obtain the adsorbed mass.

Figure 1A shows the absorbance at 230 nm (arbitrary unit) as a function of the number of deposited layer pairs. FIG. 1B represents the total mass deposited (in ng / cm 2), measured by infrared spectroscopy, as a function of the number of pairs of layers.

Example 2: Preparation of HA20C 10 / CHI-4 and HA20C 10 / PLL microbiota microcapsules Microcapsules were prepared using calcium carbonate as a biodegradable colloidal particle. These microparticles were synthesized from solutions of CaCl 2 and Na 2 CO 3 (as described by AA Antipov, D. Shchukin, Y. Fedutik, AI Petrov, GB Sukhorukov, H. Mohwald, Carbonate Microparticles for Hollow Polyelectrolyte Capsules Manufacturing, Colloids and Surfaces , A: Physicochemical and Engineering Aspects, 224 (2003) 175-183, and DV Volodkin, AI Petrov, M. Prevot, GB Sukhorukov, Matrix Polyelectrolyte Microcapsules: New System for Macromolecule Encapsulation, Langmuir, 20 (2004) 3398-3406. ). The CaCO3 microparticles were coated by the layer-by-layer deposition technique by incubating at a concentration of 2% (w / v) (as described by AI Petrov, DV Volodkin, GB Sukhorukov, Protein-Calcium Carbonate Coprecipitation: A Tool for Protein Encapsulation, Biotechnology Progress, 21 (2005) 918-925) in an aqueous solution (0.15 M NaCl, pH 6.5) HA20C10 (CI, = 1 g / l), and QCHI- 4 (CI = 2 g / l) or PLL (CI = 2 g / l). After stirring for 10 min, the microparticles were collected by centrifugation and the unadsorbed residual polyelectrolytes were removed by two washes with a 0.01 M aqueous NaCl solution (pH 6.5). After depositing 4.5 or 5 bilayers, the CaCO3 core was removed by treatment with 0.1 M EDTA solution (pH 7.2). To avoid mechanical damage to the "soft" polyelectrolyte shell, the dissolved ions resulting from CaCO3 decomposition were removed by dialysis against pure water, using Spectra / Por® dialysis membranes with a cut-off threshold of 6-8 kDa. When poly (L-lysine) is used in the multilayers with hydrophobic grafted HA, such as HA20C10 / PLL, on the CaCO3 particles, the film-coated particles are incubated with the EDC solution (400 mM) / sulfo-NHS (100 mM) at pH 6.5 for 12h, in order to crosslink the layers. The particles are then dissolved by stirring the dispersion of particles in an aqueous solution of 0.1 M EDTA (pH = 7.2). The following microcapsules were synthesized according to the protocol above: - (HA20C10 / QCHI-4) 5; (HA20C10 / QCHI-4) 4 (5 and 4 respectively indicating the number of bilayers deposited); and - (HA20C10 / PLL) 4.5.

Example 3: Inclusion of a fluorescent probe in a film This example relates to the inclusion in multilayer films of a hydrophobic fluorescence probe, Nile Red, abbreviated NR, commonly used as a hydrophobic drug model. It is known that the fluorescence of Nile Red depends on the environment in which it is located (Gautier et al., J. Controlled Release 1999, 60, 235) and that it is zero in a non-polar medium. The capacity of flat films obtained by alternating deposition of hydrophobic grafted hyaluronic acid HAlOC10 or HA20C10 and biopolymer of QCHI grafted chitosan type to trap the Nile Red was analyzed. In the present example, the probe has been pre-complexed with the hydrophobic derivatives of HA. FIG. 2 shows the measurements of the fluorescence intensity (arbitrary unit) obtained for different types of films as a function of the number of layers of hydrophobic hyaluronic acid (8 indicating 8 pairs of hydrophobic grafted QCHI / HA layers in total). The excitation and emission wavelengths for the NR are respectively 590 + 5 nm and 650 + 5 nm. More precisely, FIG. 2 shows the incorporation of Nile Red into different types of hydrophobic grafted HA / QCHI followed by spectrofluorimetry by varying the number of hydrophobic grafted HA layers with a Nile Red concentration fixed at 10 μM. It appears that HA20C10-based films have a much higher fluorescence intensity than those containing HAlOC10. This indicates that incorporation of Nile Red is greater with HA20C10 than with HAlOC10. The fluorescence of the films also increases with the degree of grafting of the quaternized chitosan, showing a synergistic effect of the two modified polysaccharides with respect to the incorporation of hydrophobic molecules.

The incorporation of hydrophobic molecules in the films can therefore be easily modulated according to the degree of grafting of the modified polysaccharides

EXAMPLE 4 Inclusion of Nile Red (Fluorescent Probe) in Capsules The capacity of these same films deposited on a biodegradable support, in this case calcium carbonate microparticles at pH 6.5, to form microcapsules was evaluated. . The derivatives tested are the capsules obtained in Example 2 (HA20C10 / QCHI-4) 5 have remarkably led to the formation of capsules after dissolution of the CaCO3 core. This method, using biocompatible particles that are easy to dissolve by treatment with a chelating agent (ethylenediaminetetraacetic acid, EDTA), thus makes it possible to obtain vectors based on novel biopolymers under mild and non-toxic conditions.

These capsules, similarly to the flat films, also have the advantage of being able to contain hydrophobic molecules insoluble in water. This is confirmed by observation in confocal microscopy microcapsules containing Nile Red in their wall. Indeed, the fluorescence observed in the walls of the capsules is a proof of their incorporation and their location in a hydrophobic environment.

Figure 3 is a confocal laser scanning microscopy image of HA20C10 / QCHI capsules (rate = 110%) containing Nile Red in the wall. The clear wall of the capsules is due to the fluorescence of the Nile Red trapped in the hydrophobic nanodomains. The shape of these capsules is spherical, and their diameter is about 5 microns, corresponding to that of CaCO3 particles. Moreover, these capsules are homogeneous in size. The images obtained by scanning electron microscopy after drying the capsules show the presence of a large number of capsules based on HA20C10. FIG. 4, scanning electron microscopy image of (HA20C10 / QCHI-4) capsules after drying, clearly shows this homogeneity. The amount of Nile Red incorporated into the capsules (HA20C10 / QCHI-4) was estimated by performing fluorescence measurements after extraction of the Nile Red from the capsules with ethanol by the following protocol. 200 μl of suspension of capsules in PBS are taken. After centrifugation (4000 rpm, 4 min, 20 ° C), the aqueous phase is removed and 0.5 mL of EtOH. After centrifugation (4000 rpm, 4 min, 20 ° C), the supernatant containing the drug is recovered. This operation is repeated twice. The alcoholic solutions are collected and analyzed using a microplate fluorescence reader (Infinite 1000, Tecan, Austria). The concentration of NR is determined using a standard curve previously established from solutions of NR in EtOH of known concentrations. The concentration per capsule is deduced from the number of capsules per mL of suspension. This is determined using a Petroff-Hausser counting chamber. The amount in each capsule deduced from the calibration curve of Nile Red in ethanol is of the order of 0.17 μg. This corresponds to a concentration per capsule of approximately 64 mM, that is to say approximately 6400 times the concentration of Nile Red in the initial aqueous solution of HA20C (CNile Red = 10 μM). In the case of chemically crosslinked capsules (HA20C10 / PLL) 4.5 (as described in Example 2), the concentration per capsule is about 3.4 mM, indicating a slightly lower incorporation capacity for these capsules. The drug release and in this case Nile Red as a function of time is determined as follows: 5 ml of a suspension of capsules in PBS are divided into 5 samples of 1 ml (J0, J2, J4, J6 and J8). In sample J0, 2 x 200 μl of suspension of capsules are taken. The two samples undergo a treatment similar to that described above for assaying the molecule incorporated in the capsules. Two samples are taken to confirm the values. Samples J2, J4, J6 and J8 are introduced into dialysis membranes (Spectra / Por® membranes with a cutoff of 6-8 kDa), and these are immersed in 200 mL of PBS. Each solution (J2, J4, J6 and J8) is washed 4 times with 200 mL PBS for 2 days. For each sample J2, J4, J6 and J8, 2 x 200 μl of suspension of capsules are taken after 2, 4, 6 and 8 days, respectively. The 2 samples undergo a treatment similar to that described above for assaying the molecule incorporated in the capsules. Analysis of the amount of Nile Red released by the capsules (HA20C10 / QCHI-4) as a function of time shows a slow release over several days, although the surrounding aqueous medium is changed twice daily. . Figure 5 shows the decrease in fluorescence intensity (in%) as a function of time (days) of the capsules (HA20C10 / QCHI-4) reflecting the release of Nile Red. This shows a high affinity of the hydrophobic molecule for the multilayer wall. This demonstrates the potential of these multilayer systems as a vector of hydrophobic active PAs.

Example 5: Inclusion of active ingredients Paclitaxel and Saquinavir Hydrophobic active ingredients were incorporated in hydrophobic grafted HA capsules and / or films and QCHI as described in Example 3: a powerful anti-cancer agent: paclitaxel (trade name for Taxol), which has proven activity against many solid human tumors and is used for the treatment of breast, ovarian and lung cancers, and 22 - a potent anti-HIV agent: Saquinavir, an HIV protease inhibitor.

Example 5a: Paclitaxel in Flat Films To study the incorporation into the films of taxol and its release, a mixture of paclitaxel and paclitaxel labeled with a fluorophore (Oregon Green) was used. Oregon Green paclitaxel concentration was set at 1 μM. The films were manufactured directly in microwells (Nunc 96-well plate) in order to read their absorbance at 230 nm and their fluorescence at the microplate reader (TECAN Infinite 1000, TECAN, Austria) (excitation wavelength 496 + 10 and 524 emission 10 + 10 nm). This mixture (Taxol and Taxol-Oregon Green), pre-supplemented with hydrophobic grafted HA, was inserted into multilayer films according to the invention, based on QCHI and hydrophobic grafted HA, as shown in FIG. 6 represents the variation of fluorescence (arbitrary unit) of Taxol-Oregon Green (A) as a function of the number of deposited layer pairs and (B) of the initial concentration of Taxol (LM) for various hydrophobic grafted HA / QCHI pairs. Thus, for an initial concentration fixed in Taxol (ranging from 1 to 10 μM), the variation of the quantity of Taxol inserted depends in part on the number of pairs of layers deposited (FIG. 6A). In addition, for a given number of layers, the amount of Taxol inserted depends both on the initial Taxol concentration during the pre-complexation and on the grafting rates of the polysaccharide pairs (FIG. 6B). Maximum efficiency is obtained for the most substituted hydrophobic grafted HA (HA20C10) in combination with the most substituted QCHI-5. It should be noted that the QCHI-4 derivative has very similar properties, whereas HAlOC10 has a lower encapsulation capacity than HA20C10.

Example 5b: Saquinavir in flat films Saquinavir, pre-supplemented with hydrophobic grafted HA, was inserted into multilayer films according to the invention, based on hydrophobic grafted QCHI-5 / HA and hydrophobic grafted PLL / HA, such as as shown in Figure 7. The initial concentration of saquinavir is 10, 50 or 100 μM.

The insertion of Saquinavir into the flat films, constructed in 96-well plates, was quantified by measuring the fluorescence of the films, due to the incorporation of Saquinavir. Indeed, it has intrinsic fluorescence properties. The fluorescence of the films was therefore measured as a function of the number of layers deposited, for films formed from PLL or QCHI-5 (FIG. 7). The excitation and emission wavelengths for Saquinavir are 239 ± 10 nm and 362 ± 10 nm, respectively. Figure 7 shows the variation in fluorescence (arbitrary unit) of Saquinavir as a function of the number of deposited layer pairs for QCHI-5 / HA hydrophobically grafted and hydrophobic grafted PLL / HA films.

Example 5c: Saquinavir in Microcapsules Saquinavir was also incorporated into microcapsules and the amount of hydrophobic drug was estimated by performing absorbance measurements using a microplate reader (TECAN) (wavelength: 239 nm) after extraction of Saquinavir capsules with methanol. The procedure is carried out according to the protocol described in Example 4. The Saquinavir concentration is determined using a standard curve previously established from solutions of known concentrations of Saquinavir in methanol. The amounts of Saquinavir, expressed per capsule, are shown in Table 1. This Table 1 shows the average amounts of Saquinavir incorporated per capsule of (HA20C10 / QCHI-4) and (HA20C10 / PLL) 4, as described by example. 2.

Table 1 0.085 0.064 inserted per capsule (pg / capsule) Amount inserted per 0.127 10-3 0.095 x 10-3 capsules (pmoFcapsule) Concentration in a 15.38 12 capsule (mM) These data demonstrate the excellent ability to incorporation of capsules into Saquinavir.

Claims (16)

REVENDICATIONS1. Material comprising, or even consisting of: - at least one acidic polysaccharide chosen from poly (galacturonate) s, heparin and its derivatives, hyaluronic acid and its derivatives, chondroitin sulphates, pectin and its derivatives, neutral polysaccharides , such as cellulose or dextran and their derivatives, modified with carboxylate and / or sulphate groups, comprising a hydrophobic unit with a molar content of at least 2% relative to the repeating unit, - at least one biopolymer cationic polymer chosen from polyamino acids and polysaccharides carrying cationic groups, chosen from mono-, di-, tri-alkylamino or tetraalkylammonium groups, this cationic biopolymer comprising a cationic molar content of at least 25% relative to the repetition unit, and optionally at least one active substance, in particular hydrophobic. 2. Material according to claim 1, characterized in that the acidic polysaccharide comprises, or even consists of hyaluronic acid and its derivatives. 3. Material according to claim 1 or 2, characterized in that the hydrophobic unit is grafted on a carboxylic acid function via an amide function, ester or - CONHNHCO-, called "carbonylhydrazide". 4. Material according to any one of claims 1 to 3, characterized in that the hydrophobic unit grafted on a carboxylic acid function is of the type - CONHNHCORI (CONHNH) mR2 where o RI represents an alkylene or a polyether, such as poly ( ethylene glycol), comprising from 1 to 17 carbon atoms, an alkenyl or an alkynyl comprising from 2 to 17 carbon atoms, an aryl comprising from 6 to 17 carbon atoms, om representing 0 or 1, where Rz representing H, a alkyl or a polyether comprising from 6 to 17 carbon atoms, an alkenyl or an alkynyl comprising from 6 to 17 carbon atoms, an aryl or an arylalkyl comprising from 6 to 17 carbon atoms. 5. Material according to any one of claims 1 to 4, characterized in that the hydrophobic unit is of the type -CONHNHCORI (CONHNH) mR2 where o RI represents - (CH2) X with x representing an integer ranging from 1 to 17 , in particular from 2 to 10, even from 3 to 8, and in particular from 4, om represents 1, where Rz represents H or an alkylene group of the - (CH2) y-CH3 type with y representing an integer ranging from 6 to at 16, in particular 7 to 14, or even 8 to 14, and in particular 9. 6. Material according to any one of claims 1 to 5, characterized in that the molar grafting rate of the hydrophobic unit ranges from 5 to 40%, especially from 10 to 30%, or even about 20% with respect to repetition unit. 7. Material according to any one of claims 1 to 6, characterized in that the cationic group is grafted via the opening of an epoxide of Formula A following Formula A in which - Ra, Rb, Rc, identical or different, represent H or an alkyl comprising from 1 to 6 carbon atoms, and in particular Ra, Rb, R1, identical or different, represent an alkyl comprising from 1 to 6 carbon atoms, - m 'is an integer ranging from 1 at 6, in particular from 1 to 4, or even 1 or 2. 8. Material according to any one of claims 1 to 7, characterized in that the biopolymer has a molar grafting rate of at least 35%, especially at least 50% relative to the number of repeating units. 25 9. Material according to any one of claims 1 to 8, characterized in that the cationic biopolymer comprises, or even consists of, chitosan bearing cationic group. 10. Material according to any one of claims 1 to 9, characterized in that the cationic biopolymer comprises, or even consists of, chitosan of formula (II): 15Formule (II) in which - n 'is a whole number ranging from 150 to 3,000, especially from 200 to 2,550, and in particular from 200 to 2,000, - R'1 and R'z represent, independently of one another, H, or -R'4NR ' aR'bR'c, with - R'4 representing a spacer of the type (CH2) x, or CHOH (CH2) X, and x 'representing an integer ranging from 1 to 6, in particular representing 1 or 2, - R a, R'b, R'c, identical or different, representing H or an alkyl comprising from 1 to 6 carbon atoms, and in particular R'a, R'b, R'c, identical or different, represent a alkyl comprising from 1 to 6 carbon atoms, or R'a, R'b, R'c, identical or different, represent an alkyl comprising 1 to 4 carbon atoms, and in particular methyl, ethyl, propyl or butyl, - R'3 represents H, an acetyl group or -R "SNR" aR "bR" c, with - R "5 representing a spacer of the type (CH2) x, or CHOH (CH2) X" and x "representing an integer ranging from from 1 to 6, in particular 1 or 2, - R "a, R" b, R "c, identical or different, representing H or an alkyl comprising from 1 to 6 carbon atoms, and in particular R" a, R "b, R" c, identical or different, represent an alkyl comprising from 1 to 6 carbon atoms, or R "a, R" b, R "c, identical or different, represent an alkyl comprising from 1 to 4 atoms of carbon, and in particular methyl, ethyl, propyl or butyl, in particular with a graft molar content of at least 25% with respect to the repeating unit. 11. Material according to any one of claims 1 to 10, characterized in that the cationic biopolymer comprises, or even consists of, poly (L-lysine), in particular said material has a crosslinking between the acid polysaccharide and the polyamino acid cationic, the crosslinking can in particular be carried out via a peptide-type bond. 12. Material according to any one of claims 1 to 11, characterized in that the active substance is selected from anti-virals, anti-cancer agents, antibiotics, anti-mycotic agents, adjuvants for vaccines. 13. Material according to any one of claims 1 to 12, characterized in that it is in the form of capsule or film. 14. A method for preparing a material as defined in any one of claims 1 to 13 comprising layer-by-layer deposition steps, and in particular alternating layers of acidic polysaccharide and cationic biopolymer. 10 15. A composition, in particular a cosmetic, pharmaceutical or food composition, for example of the food-grade type, comprising a material as claimed in any one of claims 1 to 13. Device, in particular of implantable medical implant or biomaterial type, comprising a material as claimed in any one of claims 1 to 13.