Functional amphipilic molecule or macromolecule formulations with multiple compartments

Method for preparing a formulation, with multiple compartments in the form of nanoparticles constituted by a solid core containing a therapeutic agent, surrounded by at least two lipid layers of different polarity formed from functional amphiphilic molecules or macromolecules, wherein each lipid layer is constituted by at least one functional amphiphilic compound of formula (I)

• in which
• X represents an oxygen or sulphur atom or a methylene group,
• B represents purine or pyrimidine base such as uracile, adenine, guanine, cytosine, thymine, hypoxanthine, or their derivatives, or also a non-natural mono- or bi-cyclic heterocyclic base each ring of which comprises 4 to 7 members, optionally substituted;
• L1 and L2, identical or different, represent hydrogen, an oxycarbonyl —O—C(O)— group, a thiocarbamate —O—C(S)—NH— group, a carbonate —O—C(O)—O— group, a carbamate —O—C(O)—NH— group, an oxygen atom, a phosphate group, a phosphonate group or a heteroaryl group comprising 1 to 4 nitrogen atoms, unsubstituted or substituted by a linear or branched, saturated or unsaturated, C2-C30 hydrocarbon chain, or also, L1 and L2, together, form a ketal group of formula
• or also L1 or L2 represents hydrogen, and the other represents a hydroxy group or a heteroaryl group comprising 1 to 4 nitrogen atoms, unsubstituted or substituted by a linear or branched C2-C30 alkyl chain;
• R1 and R2, identical or different, represent
• a linear or branched C2-C30 hydrocarbon chain, preferably C6-C25, in particular C8-C25, saturated or partially unsaturated, optionally completely or partially fluorinated, unsubstituted or substituted on the carbon at the end of the chain by a fluorine atom or by a benzyl or naphthyl ester or ether, or
• a diacyl chain in which each acyl chain is C2-C30, or
• a diacylglycerol, sphingosine or ceramide group, or
• when L1 or L2 represents hydrogen, and the other represents a hydroxy group or a heteroaryl group comprising 1 to 4 nitrogen atoms, R1 and R2 do not exist;
• R3 represents:
• a hydroxy, amino, phosphate, phosphonate, phosphatidylcholine, O-alkyl phosphatidylcholine, thiophosphate, phosphonium, NH2—R4, NHR4R5 or NR4R5R6 group in which R4, R5 and R6, identical or different, represent a hydrogen atom or a linear or branched C1-C5 alkyl or linear or branched C1-C5 hydroxyalkyl chain, or
• a linear or branched C2-C30 alkyl chain optionally substituted by a hydroxy group, or
• a cyclodextrin radical, or
• a
• radical in which V represents an —O—, —S—, or —NH— bond, R7 represents H or CH3, and n=1 to 500,
• or a —(CH2)n—V—R8 group, in which R8 represents a C2-C30 alkyl, and n=1 to 500, or
• a heteroaryl group containing 1 to 4 nitrogen atoms, unsubstituted or substituted by a C2-C30 alkyl, or by a (CH2)m—O—(CH2)p—R9 group in which m=1 to 6 and p=0 to 10 and R9 represents a cyclic ketal group containing 5 to 7 carbon atoms, unsubstituted or substituted by at least one linear or branched C2-C30 alkyl or by a sterol radical, or also
• R3 is linked by a covalent bond to another substituent R3, identical or different, of another compound of formula (I), identical or different, in order to form a compound of formula (I) in the form of a dimer,
• and each lipid layer has a polarity different from that of the previous one characterized in that it comprises the following steps:
• a) preparing a mixture of at least one functional amphiphilic compound of formula (I) and a therapeutic agent,
• b) subjecting said mixture to repeated heating and freezing cycles, in order to obtain nanoparticles containing said therapeutic agent, and
• c) recovering the nanoparticles containing said therapeutic agent thus obtained,
• d) bringing said nanoparticles into the presence of at least one functional amphiphilic compound of formula (I), having a polarity different from that utilized in step a), and
• e) recovering the multi-compartment nanoparticles thus obtained.