AROMATIC RING SUBSTITUTED AMPHIPHILIC POLYMERS AS DRUG DELIVERY SYSTEMS

1 . An amphiphilic block copolymer having any one of the formulas, S-[B]-H, S-[B]-H(D), D-[B]-H, S-B(D)-H, S-[B]-H-[B]-S, S-[B]-H(D)-[B]-S, D-[B]-H-[B]-S, D-[B]-H-[B]-D, S-B(D)-H-[B]-S or S-B(D)-H-B(D)-S; wherein S is a hydrophilic surface stabilizing group; B is a spacer group; H is a hydrophobic polymer or oligomer; D is a drug molecule; ( ) denotes that the group is bonded directly or indirectly as a side chain or as part of a side chain group to the adjacent group; [ ] denotes that the group is optional; and - denotes that each of the adjacent S, B, H or D are linked directly to one another or indirectly to one another via a linker group.

2 . The amphiphilic block copolymer according to claim 1 , wherein the hydrophobic polymer or oligomer comprises three or more side chain aromatic groups.

3 . The amphiphilic block copolymer according to claim 2 , wherein the hydrophobic polymer or oligomer comprises three or more side chain aromatic amine groups.

4 . The amphiphilic block copolymer according to claim 3 , wherein the aromatic amine groups have the formula —Ar—NHR, where Ar is a C6-C10 aromatic group or heterocyclic aromatic group, optionally fused to another ring, and R is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

5 . The amphiphilic block copolymer according to any one of claims 1 to 3 , wherein the hydrophobic polymer or oligomer is a poly(amino acid) comprising from about 5 to about 50 monomers.

6 . The amphiphilic block copolymer according to any one of claims 1 to 4 , wherein the hydrophobic polymer or oligomer comprises from about 3 to about 30 aromatic amino acids.

7 . The amphiphilic block copolymer according to any one of claims 1 to 6 , wherein the hydrophobic polymer or oligomer comprises a poly(amino acid)-based polymer comprised of hydrophobic monomers (e), spacer monomers (m), charged amino acid monomers (n) for charge compensation, and functional group containing monomers (o) for drug molecule (D) attachment.

8 . The amphiphilic block copolymer according to any one of claims 1 to 7 , wherein the hydrophilic surface stabilizing group comprises one or more charged functional groups.

9 . The amphiphilic block copolymer according to claim 8 , wherein the surface stabilizing group provides a high net charge (>+4, or <−4).

10 . The amphiphilic block copolymer according to any one of claims 1 to 9 , wherein the hydrophilic surface stabilizing group comprises one or more mono-saccharide or oligo-saccharide molecules.

11 . The amphiphilic block copolymer according to any one of claims 1 to 10 , wherein the drug molecule (D) has immunostimulatory properties.

12 . The amphiphilic block copolymer according to claim 11 , wherein the drug molecule (D) is a PRR agonist.

13 . The amphiphilic block copolymer according to claim 12 , wherein the drug molecule (D) is a TLR-7 agonist, a TLR-8 agonist and/or a TLR-7/8 agonist.

14 . A composition comprising the amphiphilic block copolymer according to any one of claims 1 to 13 .

15 . A particle comprising the amphiphilic block copolymer according to any one of claims 1 to 13 .

16 . A polymersome particle comprising the amphiphilic block copolymer according to any one of claims 1 to 13 .

17 . A micelle particle comprising the amphiphilic block copolymer according to any one of claims 1 to 13 .

18 . Use of the amphiphilic block copolymer according to any one of claims 1 to 13 to form a particle.

19 . Use of the amphiphilic block copolymer according to any one of claims 1 to 13 to form a polymersome particle.

20 . Use of the amphiphilic block copolymer according to any one of claims 1 to 13 to form a micelle particle.

21 . A mosaic particle comprising two or more different amphiphilic block copolymers selected from any one of the formulas, S-[B]-H, S-[B]-H(D), D-[B]-H, S-B(D)-H, S-[B]-H-[B]-S, S-[B]-H(D)-[B]-S, D-[B]-H-[B]-S, D-[B]-H-[B]-D, S-B(D)-H-[B]-S or S-B(D)-H-B(D)-S; wherein S is a hydrophilic surface stabilizing group; B is a spacer group; H is a hydrophobic polymer or oligomer; D is a drug molecule; ( ) denotes that the group is bonded directly or indirectly as a side chain or as part of a side chain group to the adjacent group; [ ] denotes that the group is optional; and - denotes that each of the adjacent S, B, H or D are linked directly to one another or indirectly to one another via a linker group.

22 . A particle of any one of claims 15 to 17 and 21 further comprising a drug molecule hydrophobic polymer or oligomer conjugate, D-H.

23 . A method of preparing particles comprising an amphiphilic block copolymer membrane and at least one drug molecule encapsulated therein, said method comprising:

providing an amphiphilic block copolymer having any one of the formulas, S-[B]-H, S-[B]-H(D), D-[B]-H, S-B(D)-H, S-[B]-H-[B]-S, S-[B]-H(D)-[B]-S, D-[B]-H-[B]-S, D-[B]-H-[B]-D, S-B(D)-H-[B]-S or S-B(D)-H-B(D)-S; wherein S is a hydrophilic surface stabilizing group; B is a spacer group; H is a hydrophobic polymer or oligomer; D is a drug molecule; ( ) denotes that the group is bonded directly or indirectly as a side chain or as part of a side chain group to the adjacent group; [ ] denotes that the group is optional; and - denotes that each of the adjacent S, B, H or D are linked directly to one another or indirectly to one another via a linker group; and

preparing an aqueous solution comprising said amphiphilic block copolymer under conditions to produce particles having the at least one drug molecule encapsulated therein.