Polymer nanoparticle composition for inducing immunity and preparation method therefor

1 . A method for inducing immunity to an active ingredient, comprising administering to a subject a composition which comprises:

a nucleic acid as the active ingredient;

a cationic compound represented by the following Formula 1; an A-B type block copolymer including a hydrophilic A block of alkylene glycol and a hydrophobic B block of polyester as an amphiphilic block copolymer; and

a salt of polylactic acid,

wherein a content of the cationic compound is 2 to 15 parts by weight, a content of the amphiphilic block copolymer is 15 to 50 parts by weight, and a content of the salt of polylactic acid is 5 to 30 parts by weight, based on 1 part by weight of the active ingredient;

wherein the active ingredient is entrapped in a nanoparticle structure of the amphiphilic block copolymer and the salt of polylactic acid,

wherein the composition is suitable for delivering the active ingredient to the spleen efficiently; and

wherein the composition is suitable for treating cancer by inducing immunity to the active ingredient:

in Formula 1,

each of n and m is independently 1 to 9, and 2≤n+m≤10,

each of a and b is 2 to 4,

each of R 1 and R 2 is independently selected from the group consisting of lauryl, myristyl, palmityl, stearyl, arachidyl, behenyl, lignoceryl, cerotyl, myristoleyl, palmitoleyl, sapienyl, oleyl, linoleyl, arachidonyl, eicosapentaenyl, erucyl, docosahexaenyl and cerotyl.

2 . The method for inducing immunity according to claim 1 , wherein the nucleic acid expresses a tumor antigen.

3 . The method for inducing immunity according to claim 2 , which is for treating a disease related to the tumor antigen.

4 . The method for inducing immunity according to claim 2 , which is for use as a vaccine against a disease related to the tumor antigen.

5 . The method for inducing immunity according to claim 1 , wherein a surface charge of the nanoparticles is −40 to 40 mV.

6 . The method for inducing immunity according to claim 1 , wherein the hydrophobic block B is modified by chemically bonding tocopherol, cholesterol or a fatty acid having 10 to 24 carbon atoms to a hydroxyl group at a terminal thereof.

7 . The method for inducing immunity according to claim 1 , wherein the hydrophilic A block has a number average molecular weight of 200 to 50,000 Dalton, and the hydrophobic B block has a number average molecular weight of 50 to 50,000 Dalton.

8 . The method according to claim 1 , wherein:

said cationic compound is at least one member selected from the group consisting of 1,6-triethylenetetramide (N,N′-((ethane-1,2-diylbis(azanediyl))bis(ethane-2,1-dioleoyl diyl))dioleamide), 1,8-dilinoleoyl tetraethylenepentamide ((9Z,9′Z,12Z,12′Z)—N,N′-(((azanediylbis(ethane-2,1-diyl))bis(azanediyl))bis(ethane-2,1-diyl))bis(octadeca-9,12-dienamide)), 1,4-dimyristoleoyl diethylenetriamide((9Z,9′Z)—N,N′-(azanediylbis(ethane-2,1-diyl))bis(tetradec-9-enamide)), 1,10-distearoyl pentaethylenehexamide (N,N′-(3,6,9,12-tetraazatetradecane-1,14-diyl)distearamide) and 1,10-dioleoyl pentaethylenehexamide (N,N′-(3,6,9,12-tetraazatetradecanc-1,14-diyl)dioleamide);

said hydrophilic A block is at least one member selected from the group consisting of polyalkyleneglycol, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylamide and derivatives thereof; and

said hydrophobic B block is at least one member selected from the group consisting of polylactide, polyglycolide, polycaprolactone, polydioxane-2-one, a copolymer of polylactide and glycolide, a copolymer of polylactide and polydioxane-2-one, a copolymer of polylactide and polycaprolactone, and a copolymer of polyglycolide and polycaprolactone.

9 . The method according to claim 1 , wherein:

said cationic compound is N,N′-((ethane-1,2-diylbis(azanediyl))bis(ethane-2,1-diyl))dioleamide;

said A-B type block copolymer is monomethoxy polyethylene glycol-polylactide block copolymer; and

said salt of polylactic acid is sodium polylactate.

10 . A method for preparing a composition for inducing immunity to an active ingredient, comprising

(a) mixing a nucleic acid as the active ingredient, a cationic compound represented by the following Formula 1, an A-B type block copolymer including a hydrophilic A block of alkylene glycol and a hydrophobic B block of polyester as an amphiphilic block copolymer and a salt of polylactic acid with a solvent which is an aqueous solution, a water-miscible organic solvent or a combination thereof; and

(b) adding an aqueous solvent to the mixture of step (a) and mixing them,

wherein a mixing amount of the cationic compound is 2 to 15 parts by weight, a mixing amount of the amphiphilic block copolymer is 15 to 50 parts by weight, and a mixing amount of the salt of polylactic acid is 5 to 30 parts by weight, based on 1 part by weight of the active ingredient;

wherein the active ingredient is entrapped in a nanoparticle structure of the amphiphilic block copolymer and the salt of polylactic acid;

wherein the composition is suitable for delivering the active ingredient to the spleen efficiently; and

wherein the composition is suitable for treating cancer by inducing immunity to the active ingredient:

in Formula 1,

each of n and m is independently 1 to 9, and 2≤n+m≤10,

each of a and b is 2 to 4,

each of R 1 and R 2 is independently selected from the group consisting of lauryl, myristyl, palmityl, stearyl, arachidyl, behenyl, lignoceryl, cerotyl, myristoleyl, palmitoleyl, sapienyl, oleyl, linoleyl, arachidonyl, eicosapentaenyl, erucyl, docosahexaenyl and cerotyl.

11 . A method for treating cancer by efficiently delivering a nucleic acid to the spleen and inducing immunity to a tumor antigen, comprising administering to a subject a composition which comprises:

a nucleic acid that expresses a tumor antigen;

a cationic compound represented by the following Formula 1;

an A-B type block copolymer including a hydrophilic A block of alkylene glycol and a hydrophobic B block of polyester as an amphiphilic block copolymer; and

a salt of polylactic acid,

wherein a content of the cationic compound is 2 to 15 parts by weight, a content of the amphiphilic block copolymer is 15 to 50 parts by weight, and a content of the salt of polylactic acid is 5 to 30 parts by weight, based on 1 part by weight of the nucleic acid;

wherein the nucleic acid is entrapped in a nanoparticle structure of the amphiphilic block copolymer and the salt of polylactic acid:

in Formula 1,

each of n and m is independently 1 to 9, and 2≤n+m≤10,

each of a and b is 2 to 4,

each of R 1 and R 2 is independently selected from the group consisting of lauryl, myristyl, palmityl, stearyl, arachidyl, behenyl, lignoceryl, cerotyl, myristoleyl, palmitoleyl, sapienyl, oleyl, linoleyl, arachidonyl, eicosapentaenyl, erucyl, docosahexaenyl and cerotyl.

12 . The method according to claim 11 , wherein said tumor antigen is a member selected from the group consisting of Trp2 (tyrosinase-related protein 2), gp100 (Glycoprotein 100), tyrosinase, PSA (Prostate-specific antigen), WT1 (Wilms' tumor 1), MAGE-1 (Melanoma-associated antigen 1), NY-ESO-1 (cancer-testis antigen), and MUC-1 (Mucin 1).

13 . The method according to claim 11 , wherein:

said cationic compound is at least one member selected from the group consisting of 1,6-dioleoyl triethylenetetramide (N,N′-((ethane-1,2-diylbis(azanediyl))bis(ethane-2,1-diyl))dioleamide), 1,8-dilinoleoyl tetraethylenepentamide ((9Z,9′Z,12Z,12′Z)—N,N′-(((azanediylbis(ethane-2,1-diyl))bis(azanediyl))bis(ethane-2,1-diyl))bis(octadeca-9,12-dienamide)), 1,4-dimyristoleoyl diethylenetriamide((9Z,9′Z)—N,N′-(azanediylbis(ethane-2,1-diyl))bis(tetradec-9-enamide)), 1,10-distearoyl pentaethylenehexamide (N,N′-(3,6,9,12-tetraazatetradecane-1,14-diyl)distearamide) and 1,10-dioleoyl pentaethylenehexamide (N,N′-(3,6,9,12-tetraazatetradecane-1,14-diyl)dioleamide);

said hydrophilic A block is at least one member selected from the group consisting of polyalkyleneglycol, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylamide and derivatives thereof; and

said hydrophobic B block is at least one member selected from the group consisting of polylactide, polyglycolide, polycaprolactone, polydioxane-2-one, a copolymer of polylactide and glycolide, a copolymer of polylactide and polydioxane-2-one, a copolymer of polylactide and polycaprolactone, and a copolymer of polyglycolide and polycaprolactone.

14 . The method according to claim 11 , wherein:

said cationic compound is N,N′-((ethane-1,2-diylbis(azanediyl))bis(ethane-2,1-diyl))diolcamide;

said A-B type block copolymer is monomethoxy polyethylene glycol-polylactide block copolymer; and

said salt of polylactic acid is sodium polylactate.

15 . The method according to claim 14 , wherein a surface charge of the nanoparticles is −40 to 40 m V.

16 . The method for inducing immunity according to claim 11 , wherein a surface charge of the nanoparticles is-40 to 40 mV.