BLOCK-COPOLYMERS FOR THE DELIVERY OF ACTIVE AGENTS

Abstract

Provided is an (A)-(B)-(A) triblock copolymer comprising two hydrophilic polymer blocks (A) as further defined herein, and a polymer block (B), said polymer block (B) comprising at least one type of repeating unit of the following formula (I) wherein R.sup.1 is an aliphatic hydrocarbon group which is optionally substituted with one or more of —OR.sup.5, —SR.sup.5, —NR.sup.6R.sup.7, —(NR.sup.6R.sup.7R.sup.8)+, —CONR.sup.6R.sup.7, —C(O)OR.sup.9 and —C(O)R.sup.10, wherein R.sup.5 to R.sup.10 are independently selected from H, aliphatic and aromatic residues, and wherein R.sup.1 is selected such that the polymer block (B) is more hydrophobic than the polymer block (A); and compositions, such as pharmaceutical compositions, formed with the block copolymer.

##STR00001##

Claims

1. An (A)-(B)-(A) triblock copolymer comprising two hydrophilic polymer blocks (A), which are independently selected from (i) a polymer block (A) formed from at least one type of the repeating units of the following formula (II) ##STR00044## wherein R.sup.2 is an aliphatic hydrocarbon group which is optionally substituted with one or more of —OR.sup.11, —SR.sup.11, —NR.sup.11R.sup.12, —(NR.sup.11R.sup.12R.sup.13).sup.+, —CONR.sup.11R.sup.12, —C(O)OR.sup.14 and —C(O)R.sup.15, wherein R.sup.11 to R.sup.15 are independently selected from H and C1-C3 alkyl, and wherein the aliphatic hydrocarbon group and the optional substituents are selected such that the resulting polymer block (A) is hydrophilic; (ii) a polymer block (A) formed from at least one type of the repeating units of the following formula (III) ##STR00045## wherein R.sup.3 is selected from a methyl and an ethyl group, which groups are optionally substituted with one or more of —OR.sup.11, —SR.sup.11, —NR.sup.11R.sup.12, —(NR.sup.11R.sup.12R.sup.13).sup.+, —CONR.sup.11R.sup.12, —C(O)OR.sup.14 and —C(O)R.sup.15, wherein R.sup.11 to R.sup.15 are independently selected from H and C1-C3 alkyl and wherein the optional substituents, if present, are selected such that the resulting polymer block (A) is hydrophilic; and (iii) a polymer block (A) formed from at least one type of the repeating units of formula (II) and at least one type of the repeating units of formula (III) as defined above, and a polymer block (B), said polymer block (B) comprising at least one type of repeating unit of the following formula (I) ##STR00046## wherein R.sup.1 is an aliphatic hydrocarbon group which is optionally substituted with one or more of —OR.sup.5, —SR.sup.5, —NR.sup.6R.sup.7, —(NR.sup.6R.sup.7R.sup.8).sup.+, —C(O)OR.sup.9, —CONR.sup.6R.sup.7 and —C(O)R.sup.10, wherein R.sup.5 to R.sup.10 are independently selected from H, aliphatic or aromatic residues, and wherein R.sup.1 is selected such that the polymer block (B) is more hydrophobic than the polymer block (A).

2. The triblock copolymer of claim 1, wherein the hydrophilic polymer blocks (A) are independently formed from at least one type of the repeating units of the following formula (II) ##STR00047## wherein R.sup.2 is an aliphatic hydrocarbon group which is optionally substituted with one or more of —OR.sup.11, —SR.sup.11, —NR.sup.11R.sup.12, —(NR.sup.11R.sup.12R.sup.13).sup.+, —CONR.sup.11R.sup.12, —C(O)OR.sup.14 and —C(O)R.sup.15, wherein R.sup.11 to R.sup.15 are independently selected from H and C1-C3 alkyl.

3. The triblock copolymer of claim 1, wherein R.sup.2 is an optionally substituted alkyl group.

4. The triblock copolymer of claim 3, wherein R.sup.2 is an optionally substituted methyl or ethyl group.

5. The triblock copolymer of claim 2, wherein R.sup.2 is a non-substituted methyl group or a non-substituted ethyl group.

6. The triblock copolymer of claim 1, wherein R.sup.3 is a non-substituted methyl group or a non-substituted ethyl group.

7. The triblock copolymer of claim 1, wherein R.sup.1 in the repeating units of formula (I) is an optionally substituted aliphatic C3-C20 hydrocarbon group.

8. The triblock copolymer of claim 1, wherein R.sup.1 in the repeating units of formula (I) is an optionally substituted C3-C20 alkyl group.

9. The triblock copolymer of claim 1, wherein R.sup.1 in the repeating units of formula (I) is an optionally substituted C3-C9 alkyl group.

10. The triblock copolymer of claim 1, wherein R.sup.1 in the repeating units of formula (I) is an optionally substituted C3-C5 alkyl group.

11. The triblock copolymer of claim 1, wherein R.sup.1 in the repeating units of formula (I) is a propyl or a butyl group.

12. The triblock copolymer of claim 1, wherein the repeating units of formula (I) provide 50% or more of the repeating units of the polymer block (B), in terms of the number of repeating units of formula (I) with respect to the total number of repeating units in the block (B) as 100%.

13. The triblock copolymer of claim 1, wherein the polymer block (B) further comprises a repeating unit of the following formula (IV) ##STR00048## wherein R.sup.4 represents a C3-C20 alkyl group.

14. The triblock copolymer of claim 1, wherein the polymer block (B) is selected from (i) a polymer block (B) formed from at least one type of the repeating units of formula (I) ##STR00049## wherein R.sup.1 represents a C3-C9 alkyl group; and (ii) a polymer block (B) formed from 50% or more, in terms of the number of repeating units and based on the total number of repeating units in the polymer block as 100%, of repeating units of formula (I) as shown above, wherein R.sup.1 represents a C3-C9 alkyl group, and 50% or less, in terms of the number of repeating units and based on the total number of repeating units in the polymer block as 100%, of repeating units of formula (IV) ##STR00050## wherein R.sup.4 represents a C3-C7 alkyl group, and wherein the sum of the number of the repeating units of formula (I) and of formula (IV) is 100%.

15. The triblock copolymer of claim 1, wherein the polymer block (B) is formed from at least one type of the repeating units of formula (I) ##STR00051## wherein R.sup.1 represents a C3-C9 alkyl group.

16. The triblock copolymer of any of claim 1, wherein the polymer blocks (A) and the polymer block (B) are each formed from a single type of repeating unit.

17. A composition comprising one or more triblock copolymers as defined in claim 1 in combination with one or more compounds to be solubilized.

18. The composition of claim 17, wherein the one or more compounds to be solubilized are characterized by a solubility in distilled water at a temperature of 25° C. of not more than 1 g/l.

19. The composition of claim 17, wherein the weight ratio of the weight of the compound(s) to be solubilized to the weight of the triblock copolymer(s) is at least 0.1:1.0.

20. The composition of claim 17, which is a solid composition.

21. The composition of claim 20, wherein the triblock copolymer(s) and the compound(s) to be solubilized form a solid solution.

22. The composition of claim 17, which is a solution, an emulsion or a suspension.

23. The composition of claim 22, which is an aqueous solution, aqueous emulsion or aqueous suspension.

24. The composition of claim 22, wherein the composition comprises micelles which are formed by the triblock copolymer(s) and which incorporate the compound(s) to be solubilized.

25. The composition of claim 17, wherein the one or more triblock copolymers form micelles which incorporate the compound(s) to be solubilized.

26. The composition of claim 17, wherein the one or more compounds to be solubilized are active agents.

27. The composition of claim 17, wherein the one or more compounds to be solubilized are selected from therapeutically active agents, agents for use in diagnosis, fungicides, pesticides, insecticides, herbicides, phytohormones and catalytically active compounds.

28. The composition of claim 17, which is a pharmaceutical composition which comprises one or more therapeutically active agents as the compound(s) to be solubilized.

29. The composition of claim 28, wherein the therapeutically active agent comprises a chemotherapeutic agent which is suitable for the treatment of cancer.

30. A method for treatment of cancer, comprising administrating a therapeutically effective amount of a composition of claim 29 to a patient in need thereof.

31. A method for the preparation of a pharmaceutical composition, said method comprising the step of combining a triblock copolymer of claim 1 with one or more therapeutically active agent as compounds to be solubilized.

32. (canceled)

33. A method for solubilizing one or more compounds in an aqueous environment, comprising the step of incorporating the compound(s) as compounds to be solubilized into a composition of claim 17.

34. The method of claim 33, wherein the aqueous environment comprises a liquid phase with a content of water of more than 50% (vol./vol.) or a hydrogel.

35. A method for the detection of one or more compounds which interact with a target of interest in a screening test, said method comprising the steps of providing one or more compounds to be subjected to the detection method, separately incorporating the compound(s) as compounds to be solubilized each into a composition as defined in claim 17, and subjecting the compositions to the screening test.

36. The method of claim 33, wherein the one or more compounds are characterized by a solubility in distilled water at a temperature of 25° C. of not more than 1 g/l.

Description

EXAMPLES

Reagents and Solvents

[0238] All substances for the preparation of the polymers were purchased from Sigma-Aldrich (Steinheim, Germany) or Acros (Geel, Belgium) and were used as received unless otherwise stated. Curcumin powder from Curcuma longa (Turmeric) (curcumin ≥65%; (curcumin=79%; demethoxycurcumin=17%, bisdemethoxycurcumin=4%; determined by HPLC)) and Atorvastatin calcium salt trihydrate 98%; HPLC) were purchased from Sigma-Aldrich. Paclitaxel was purchased from LC Laboratories (Woburn, Mass., USA). Deuterated solvents for NMR analysis were obtained from Deutero GmbH (Kastellaun, Germany).

[0239] The monomers BuOx, BuOzi and PrOzi were prepared following the procedure by Seeliger et al. (H. Witte, W. Seeliger, Justus Liebigs Annalen der Chemie 1974, 1974, 996-1009). The monomers EtHepOx and EtHepOzi were prepared following the procedure by Kempe et al. (K. Kempe, S. Jacobs, H. M. L. Lambermont-Thijs, M. M. W. M. Fijten, R. Hoogenboom, U. S. Schubert, Macromolecules 2010, 43, 4098-4104). The monomers NonOx and NonOzi were prepared following the procedure by M. Beck et al. (M. Beck, P. Birnbrich, U. Eicken, H. Fischer, W. E. Fristad, B. Hase, H.-J. Krause, Die Angewandte Makromolekulare Chemie 1994, 223, 217-233).

[0240] All substances used for polymerization, methyl trifluoromethylsufonate (MeOTf), propargyl p-toluenesulfonate, MeOx, BuOx, PrOzi, BuOzi, EtHepOx, EtHepOzi, NonOx, NonOzi, benzonitrile (PhCN), sulfolane, acetonitrile, and other solvents for polymer preparation were refluxed over CaH.sub.2 and distilled under argon.

Syntheses

Living Cationic Ring-Opening Polymerization, General Synthetic Procedure 1 (GSP1)

[0241] The polymerizations and work-up procedures were carried out as described previously (R. Luxenhofer, R. Jordan, Macromolecules 2006, 39, 3509-3516). Exemplary, the preparation of Prop-MeOx.sub.35-b-PrOzi.sub.20-b-MeOx.sub.35-PipBoc was performed as follows:

Prop-MeOx.sub.35-b-PrOzi.sub.20-b-MeOx.sub.35-PipBoc

##STR00029##

[0242] Under dry and inert conditions, 0.37 g (1.75 mmol, 1 eq) propargyl p-toluenesulfonate and 5.19 g (61.0 mmol, 35 eq) 2-methyl-2-oxazoline (MeOx) were dissolved in 35 mL dry sulfolane at room temperature. The mixture was stirred for 16 h at 90° C. After cooling to RT, the monomer for the second block, 2-n-propyl-2-oxazine (4.41 g, 34.7 mmol, 20 eq) was added and the mixture was stirred for 20 h at 100° C. The procedure was repeated for the third block with 5.19 g (70.0 mmol, 35 eq) MeOx. Termination was carried out with 0.97 g of 1-BOC-piperazine (5.23 mmol, 3 eq) at 50° C. overnight. K.sub.2CO.sub.3 (0.24 g, 1.74 mmol, 1 eq) was added and the mixture was stirred at 50° C. overnight. Precipitates were removed by centrifugation. The supernatant was transferred into a dialysis bag (MWCO 1 kDa) and dialyzed against Millipore water (1 L) overnight. The solution was recovered from the bag and lyophilized.

TABLE-US-00002 Yield 10.2 g (1.17 mmol; 67%) of a white powder M 8.7 kg/mol GPC (DMF) M.sub.n = 6.1 kg/mol; Ð (dispersity, determined via GPC) = 1.16 .sup.1H-NMR M.sub.n = 9.8 kg/mol (Prop-MeOx.sub.38-b-PrOzi.sub.23-b-MeOx.sub.38-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 4.33-4.02 (br, 2H, alkyne-CH.sub.2—N); 3.70-3.37 (br, 319H, (N—CH.sub.2CH.sub.2); 3.37-3.15 (br, 102H, N—CH.sub.2—CH.sub.2—CH.sub.2—); 2.56-2.34 (br, 4H, pip—CH.sub.2—CH.sub.2—); 2.32-2.19 (br, 39H, CO—CH.sub.2—CH.sub.2—CH.sub.3); 2.19-1.99 (br, 230H, CO—CH.sub.3); 1.95-1.55 (br, 163H, N—CH.sub.2—CH.sub.2—CH.sub.2—; CO—CH.sub.2—CH.sub.2—CH.sub.3); 1.04-0.87 (br, 70H, CO—CH.sub.2—CH.sub.2—CH.sub.3).
Prop-MeOx.sub.35-b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc

##STR00030##

[0243] Prop-MeOx.sub.35-b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc was synthesized according to GSP 1

TABLE-US-00003 Initiation: PrOTs 1.10 g (5.22 mmol; 1 eq) 1. Block: MeOx 15.6 g (0.18 mol; 35 eq) 2. Block: BuOzi 13.3 g (0.10 mol; 20 eq) 3. Block: MeOx 15.5 g (0.18 mol; 35 eq) Termination: Boc-Pip  3.0 g (16.1 mmol; 3 eq) Solvent Sulfolane 120 mL Yield 31.4 g (3.5 mmol; 69%) of a white powder M 9.0 kg/mol GPC (DMF) M.sub.n = 5.6 kg/mol; Ð = 1.20 .sup.1H-NMR M.sub.n = 13.3 kg/mol (Prop-MeOx.sub.52-b-BuOzi.sub.30-b-MeOx.sub.52-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 4.30-4.00 (br, 2H, alkyne- CH.sub.2—N); 3.85-3.36 (br, 419H, (N—CH.sub.2CH.sub.2); 3.36-2.94 (br, 134H, N—CH.sub.2—CH.sub.2—CH.sub.2); 2.38-2.16 (br, 103H, CO—CH.sub.2—CH.sub.2—CH.sub.2—CH.sub.3); 2.17-1.92 (br, 310H, CO—CH.sub.3); 1.92-1.67 (br, 50H, N—CH.sub.2—CH.sub.2—CH.sub.2—); 1.67-1.46 (br, 57H, CO—CH.sub.2—CH.sub.2—CH.sub.2—CH.sub.3); 1.40-1.89 (br, 60H, CO—(CH.sub.2).sub.2—CH.sub.2—CH.sub.3); 1.00-0.76 (br, 90H, CO—(CH.sub.2).sub.3—CH.sub.3).
Prop-MeOx.sub.35-b-BuOx.sub.20-b-MeOx.sub.35-Pip (Reference Polymer)

##STR00031##

[0244] Prop-MeOx.sub.35-b-BuOx.sub.20-b-MeOx.sub.35-Pip was synthesized according to GSP 1

TABLE-US-00004 Initiation: PrOTs 0.38 g (1.77 mmol; 1 eq) 1. Block: MeOx 5.35 g (6.18 mol; 35 eq) 2. Block: BuOx 4.59 g (3.53 mol; 20 eq) 3. Block: MeOx 5.34 g (6.18 mol; 35 eq) Termination: Pip 3.04 g (1.77 mmol; 3 eq) Solvent PhCl/ACN = 1/1 (v/v) 120 mL Yield 12.3 g (0.14 mmol; 82%) of a white powder M 8.5 kg/mol GPC (DMF) M.sub.n = 5.8 kg/mol; Ð = 1.19 .sup.1H-NMR M.sub.n = 11.6 kg/mol (Prop-MeOx.sub.45-b-BuOx.sub.30-b-MeOx.sub.45-Pip) (CDCl.sub.3, 300.12 MHz; 298K): δ = 4.30-4.00 (br, 2H, alkyne- CH.sub.2—N); 3.85-3.36 (br, 482H, (N—CH.sub.2CH.sub.2); 2.39-1.90 (br, 355H, CO—CH.sub.3; CO—CH.sub.2—(CH.sub.2).sub.2—CH.sub.3); 1.65-1.46 (br, 58H, CO—CH.sub.2—CH.sub.2—CH.sub.2—CH.sub.3); 1.40-1.26 (br, 59H, CO—(CH.sub.2).sub.2—CH.sub.2—CH.sub.3); 0.97-0.83 (br, 89H, CO—(CH.sub.2).sub.3—CH.sub.3).
Me-MeOzi.sub.36-PrOzi.sub.18-MeOzi.sub.36-PipBoc

##STR00032##

[0245] Me-MeOzi.sub.36-PrOzi.sub.18-MeOzi.sub.35-PipBoc was synthesized according to GSP 1

TABLE-US-00005 Initiation: MeOTf 0.06 g (0.35 mmol; 1 eq) 1. Block: MeOzi 1.25 g (12.6 mmol; 36 eq) 2. Block: PrOzi 0.81 g (6.37 mmol; 18 eq) 3. Block: MeOzi 1.22 g (12.3 mmol; 35 eq) Termination: PipBoc 0.20 g (1.05 mmol; 3 eq) Solvent PhCN 7 mL Yield 2.02 g (0.21 mmol; 59%) of a white powder M 9.5 kg/mol GPC (HFIP) M.sub.n = 5.6 kg/mol; Ð = 1.29 .sup.1H-NMR M.sub.n = 11.0 kg/mol (Me-MeOzi.sub.41-b-PrOzi.sub.21-b-MeOzi.sub.41-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.55-3.12 (br, 397H, N—CH.sub.2—CH.sub.2—CH.sub.2); 3.04-3.00 (br, 3H, CH.sub.3—N); 2.31-2.17 (br, 44H, CO—CH.sub.2—CH.sub.2—CH.sub.3); 2.17-2.00 (br, 247H, CO—CH.sub.3); 1.93-1.53 (br, 243H, CO—CH.sub.2—CH.sub.2—CH.sub.2—CH.sub.3; N—CH.sub.2—CH.sub.2—CH.sub.2); 1.46-1.41 (br, 6H, -PipBoc); 1.00-0.84 (br, 62H, CO—(CH.sub.2)2—CH.sub.3).
Me-MeOx.sub.35-NonOx.sub.12-MeOx.sub.35-PipBoc (Reference Polymer)

##STR00033##

[0246] Me-MeOx.sub.35-NonOx.sub.12-MeOx.sub.35-PipBoc was synthesized according to GSP 1

TABLE-US-00006 Initiation: MeOTf 0.15 g (0.9 mmol; 1 eq) 1. Block: MeOx 2.69 g (31.9 mol; 35 eq) 2. Block: NonOx 2.14 g (10.9 mol; 12 eq) 3. Block: MeOx 2.68 g (31.5 mol; 35 eq) Termination: PipBoc 0.51 g (2.7 mmol; 3 eq) Solvent PhCN 16 mL Yield: 6.47 g (0.76 mmol; 84%) of a white powder M 8.5 kg/mol GPC (HFIP) M.sub.n = 5.1 kg/mol; Ð = 1.16 .sup.1H-NMR M.sub.n = 8.3 kg/mol (Me-MeOx.sub.33-b-NonOx.sub.11-b-MeOx.sub.33-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.58-3.31 (br, 305H, N—CH.sub.2—CH.sub.2); 3.07-2.93 (br, 3H, CH.sub.3—N); 2.37-2.18 (br, 23H, CO—CH.sub.2—(CH.sub.2).sub.7—CH.sub.3); 2.18-1.98 (br, 199H, CO—CH.sub.3); 1.67-1.49 (br, 23H, CO—CH.sub.2—CH.sub.2—(CH.sub.2).sub.6—CH.sub.3); 1.48-1.42 (br, 10H, -PipBoc); 1.36-1.15 (br, 137H, CO—(CH.sub.2).sub.2—(CH.sub.2).sub.6—CH.sub.3; 0.92-0.80 (br, 34H, CO—(CH.sub.2).sub.8—CH.sub.3).
Me-MeOx.sub.35-NonOzi.sub.11-MeOx.sub.35-PipBoc

##STR00034##

[0247] Me-MeOx.sub.35-NonOzi.sub.11-MeOx.sub.35-PipBoc was synthesized according to GSP 1

TABLE-US-00007 Initiation: MeOTf 0.14 g (0.9 mmol; 1 eq) 1. Block: MeOx 2.58 g (6.18 mol; 35 eq) 2. Block: NonOzi 2.05 g (3.53 mol; 11 eq) 3. Block: MeOx 2.58 g (6.18 mol; 35 eq) Termination: PipBoc 0.49 g (1.77 mmol; 3 eq) Solvent PhCN 16 mL Yield: 6.92 g (0.8 mmol; 94%) of a white powder M 8.5 kg/mol GPC (HFIP) M.sub.n = 4.6 kg/mol; Ð = 1.22 .sup.1H-NMR M.sub.n = 6.5 kg/mol (Me-MeOx.sub.27-b-NonOzi.sub.8-b-MeOx.sub.27-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.58-3.36 (br, 214H, N—CH.sub.2—CH.sub.2); 3.36-3.18 (br, 34H, N—CH.sub.2—CH.sub.2—CH.sub.2); 3.07-2.94 (br, 3H, CH.sub.3—N); 2.34-2.19 (br, 16H, CO—CH.sub.2—(CH.sub.2).sub.7—CH.sub.3); 2.19-1.97 (br, 162H, CO—CH.sub.3); 1.89-1.69 (br, 31H, CO—CH.sub.2—CH.sub.2—(CH.sub.2).sub.6—CH.sub.3); 1.69-1.50 (br, 42H, N—CH.sub.2—CH.sub.2—CH.sub.2); 1.48-1.42 (br, 7H, PipBoc); 1.37-1.18 (br, 96H, CO—(CH.sub.2).sub.2—(CH.sub.2).sub.6—CH.sub.3; 0.93-0.81 (br, 24H, CO—(CH.sub.2).sub.8—CH.sub.3).
Me-MeOx.sub.36-EtHepOx.sub.13-MeOx.sub.36-PipBoc (Reference Polymer)

##STR00035##

[0248] Me-MeOx.sub.36-EtHepOx.sub.13-MeOx.sub.36-PipBoc was synthesized according to GSP 1

TABLE-US-00008 Initiation: MeOTf 0.27 g (1.63 mmol; 1 eq) 1. Block: MeOx  5.0 g (58.8 mol; 36 eq) 2. Block: EtHepOx 4.08 g (2.07 mol; 13 eq) 3. Block: MeOx 5.03 g (59.1 mol; 36 eq) Termination: PipBoc 0.91 g (4.89 mmol; 3 eq) Solvent PhCN 30 mL Yield: 12.7 g (1.43 mmol; 88%) of a white powder M 8.9 kg/mol GPC (HFIP) M.sub.n = 4.9 kg/mol; Ð = 1.16 .sup.1H-NMR M.sub.n = 8.9 kg/mol (Me-MeOx.sub.37-b-EtHepOx.sub.12-b-MeOx.sub.37-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.80-3.14 (br, 339H, N—CH.sub.2—CH.sub.2); 3.07-2.92 (br, 3H, CH.sub.3—N); 2.38-2.23 (br, 14H, CO—(CH.sub.2)—CH.sub.2—CH—) 2.23-1.99 (br, 223H, CO—CH.sub.3); 2.00-1.75 (br, 11H, CO—(CH.sub.2).sub.2—CH—); 1.46-1.41 (br, 9H, -PipBoc); 1.36-1.14 (br, 112H, CO—(CH.sub.2).sub.2—CH—CH.sub.2—CH.sub.3; CO—(CH.sub.2).sub.2—CH—(CH.sub.2).sub.3—CH.sub.3 0.94-0.76 (br, 75H, CO—(CH.sub.2).sub.2—CH—CH.sub.2—CH.sub.3; CO—(CH.sub.2).sub.2—CH—(CH.sub.2).sub.3—CH.sub.3).
Me-MeOx.sub.36-EtHepOzi.sub.11-MeOx.sub.36-PipBoc

##STR00036##

[0249] Me-MeOx.sub.36-EtHepOzi.sub.11-MeOx.sub.36-PipBoc was synthesized according to GSP 1

TABLE-US-00009 Initiation: MeOTf 0.28 g (1.71 mmol; 1 eq) 1. Block: MeOx 5.16 g (60.7 mol; 36 eq) 2. Block: EtHepOzi 4.02 g (19.1 mol; 11 eq) 3. Block: MeOx 5.17 g (60.8 mol; 36 eq) Termination: PipBoc 0.96 g (5.13 mmol; 3 eq) Solvent PhCN 30 mL Yield 13.3 g (1.53 mmol; 89%) of a white powder M 9.7 kg/mol GPC (HFIP) M.sub.n = 4.4 kg/mol; Ð = 1.15 .sup.1H-NMR M.sub.n = 9.5 kg/mol (Me-MeOx.sub.40-b-EtHepOzi.sub.12-b-MeOx.sub.40-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.75-3.36 (br, 322H, N—CH.sub.2—CH.sub.2); 3.35-3.16 (br, 49H, N—CH.sub.2—CH.sub.2—CH.sub.2) 3.09-2.92 (br, 3H, CH.sub.3—N); 2.35-2.19 (br, 22H, CO—(CH.sub.2)—CH.sub.2—CH—) 2.18-2.00 (br, 240H, CO—CH.sub.3); 1.98-1.70 (br, 45H, CO—(CH.sub.2).sub.2—CH—; N—CH.sub.2—CH.sub.2—CH.sub.2—); 1.46-1.43 (br, 10H, -PipBoc); 1.37-1.12 (br, 106H, CO—(CH.sub.2).sub.2—CH—CH.sub.2—CH.sub.3; CO—(CH.sub.2).sub.2—CH—(CH.sub.2).sub.3—CH.sub.3 0.97-0.76 (br, 72H, CO—(CH.sub.2).sub.2—CH—CH.sub.2—CH.sub.3; CO—(CH.sub.2).sub.2—CH—(CH.sub.2).sub.3—CH.sub.3).
Me-MeOx.sub.35-PrOzi.sub.20-MeOx.sub.35-PipBoc

##STR00037##

[0250] Me-MeOx.sub.35-PrOzi.sub.20-MeOx.sub.35-PipBoc was synthesized according to GSP 1

TABLE-US-00010 Initiation: MeOTf 0.96 g (5.85 mmol, 1 eq), 1. Block: MeOx 17.6 g (0.21 mol, 35 eq) 2. Block: PrOzi 15.0 g (0.12 mol, 20 eq) 3. Block: MeOx 17.6 g (0.21 mol, 35 eq) Termination: Boc-Pip 3.27 g (17.6 mmol, 3 eq) K.sub.2CO.sub.3 0.81 g (5.85 mmol, 1 eq) Solvent PhCN 120 mL Yield: 37.1 g (4.4 mmol; 75%) of a white powder M.sub.w 8.4 kg/mol .sup.1H-NMR M.sub.n = 8.2 kg/mol (Me-MeOx.sub.33-b-PrOzi.sub.19-b-MeOx.sub.33-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.78-3.37 (br, 258H, H.sup.1); 3.37-3.15 (br, 81H H.sup.2); 3.09-3.02 (br, 3H, H.sup.3), 2.35-2.19 (br, 39H, H.sup.4); 2.19-2.00 (br, 197H, H.sup.5); 1.92-1.73 (br, 37H, H.sup.6), 1.73-1.51 (br, 57H, H.sup.7); 1.50-1.41 (s, 9H, H.sup.8); 1.05-0.83 (br, 58H, H.sup.9).
Me-MeOx.sub.35-b-iPrOzi.sub.18-b-MeOx.sub.35-PipBoc

##STR00038##

[0251] Me-MeOx.sub.35-b-iPrOzi.sub.20-b-MeOx.sub.35-PipBoc was synthesized according to GSP 1

TABLE-US-00011 Initiation: MeOTf 0.26 g (1.6 mmol; 1 eq) 1. Block: MeOx  4.7 g (55.2 mmol; 35 eq) 2. Block: iPrOzi 3.59 g (28.2 mmol; 18 eq) 3. Block: MeOx 4.77 g (56.1 mmol; 35 eq) Termination: Boc-Pip 0.88 g (4.7 mmol; 3 eq) Solvent PhCN 29 mL Yield 8.98 g (1.06 mmol; 67%) of a white powder M 8.4 kg/mol GPC (DMF) M.sub.n = 5.9 kg/mol; Ð = 1.26 .sup.1H-NMR M.sub.n = 7.3 kg/mol (Me-MeOx.sub.30-b-iPrOzi.sub.16-b-MeOx.sub.30-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.59-3.36 (br, 243H, N—CH.sub.2CH.sub.2); 3.36-3.19 (br, 66H, N—CH.sub.2—CH.sub.2—CH.sub.2—); 3.08-2.93 (m, 3H, N—CH.sub.3); 2.77-2.60 (br, 15H, CO—CH—(CH.sub.3).sub.2); 2.46-2.40 (br, 2H, —CH.sub.2N—(CH.sub.2).sub.2—(Pip)); 2.20-2.00 (m, 182H, CO—CH.sub.3); 1.91-1.65 (br, 42H, N—CH.sub.2—CH.sub.2—CH.sub.2—); 1.48-1.42 (m, 10H, —C—(CH.sub.3).sub.3); 1.18-1.01 (m, 117H, CO—CH—(CH.sub.3).sub.2) ppm.
Me-MeOx.sub.34-b-iPrOx.sub.20-b-MeOx.sub.35-PipBoc (Reference Polymer)

##STR00039##

[0252] Me-MeOx.sub.35-b-iPrOx.sub.20-b-MeOx.sub.35-PipBoc was synthesized according to GSP 1

TABLE-US-00012 Initiation: MeOTf 0.18 g (1.1 mmol; 1 eq) 1. Block: MeOx 3.28 g (38.6 mmol; 34 eq) 2. Block: iPrOx 2.57 g (22.8 mmol; 20 eq) 3. Block: MeOx 3.38 g (39.7 mmol; 35 eq) Termination: Boc-Pip 0.68 g (3.7 mmol; 3 eq) Solvent PhCN 29 mL Yield 8.46 g (1.0 mmol; 90%) of a white powder M 8.4 kg/mol GPC (DMF) M.sub.n = 6.2 kg/mol; Ð = 1.20 .sup.1H-NMR M.sub.n = 7.9 kg/mol (Me-MeOx.sub.33-b-iPrOx.sub.20-b-MeOx.sub.33-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.58-3.31 (br, 345H, N—CH.sub.2CH.sub.2); 3.09-3.01 (m, 3H, N—CH.sub.3); 2.46-2.40 (br, 2H, —CH.sub.2N—(CH.sub.2).sub.2—(Pip)); 2.20-1.98 (m, 201H, CO—CH.sub.3); 1.88-1.77 (br, 26H, CO—CH—(CH.sub.3).sub.2; 1.48-1.42 (m, 9H, —C—(CH.sub.3).sub.3); 1.18-1.01 (m, 117H, CO—CH—(CH.sub.3).sub.2) ppm.
Me-MeOx.sub.36-b-cPrOzi.sub.18-b-MeOx.sub.36-PipBoc

##STR00040##

[0253] Me-MeOx.sub.36-b-cPrOzi.sub.18-b-MeOx.sub.36-PipBoc was synthesized according to GSP 1

TABLE-US-00013 Initiation: MeOTf 0.43 g (2.61 mmol; 1 eq) 1. Block: MeOx 7.94 g (93.3 mmol; 36 eq) 2. Block: cPrOzi  6.0 g (47.9 mmol; 18 eq) 3. Block: MeOx 7.90 g (92.8 mmol; 36 eq) Termination: Boc-Pip 1.46 g (7.83 mmol; 3 eq) K.sub.2CO.sub.3 0.44 g (2.61 mmol; 1 eq) Solvent PhCN 50 mL Yield 17.07 g (1.98 mmol; 67%) of a white powder M 8.6 kg/mol GPC (HFIP) M.sub.n = 4.8 kg/mol; Ð = 1.23 .sup.1H-NMR M.sub.n = 8.1 kg/mol (Me-MeOx.sub.34-b-cPrOzi.sub.17-b-MeOx.sub.34-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.76-3.19 (br, 327H, N—CH.sub.2CH.sub.2, N—CH.sub.2—CH.sub.2—CH.sub.2—); 3.07-2.90 (m, 3H, N—CH.sub.3); 2.56-2.36 (br, 4H, —CH.sub.2N—(CH.sub.2).sub.2—(Pip)); 2.21-1.94 (m, 203H, CO—CH.sub.3); 1.95-1.53 (br, 48H, N—CO—CH—(CH).sub.2, N—CH.sub.2—CH.sub.2—CH.sub.2—); 1.48-1.39 (s, 9H, —C—(CH.sub.3).sub.3); 1.04-0.60 (d, 67H, CO—CH—(CH.sub.2).sub.2) ppm.
Me-MeOx.sub.35-b-cPrOx.sub.18-b-MeOx.sub.35-PipBoc (Reference Polymer)

##STR00041##

[0254] Me-MeOx.sub.35-b-cPrOx.sub.18-b-MeOx.sub.35-PipBoc was synthesized according to GSP 1

TABLE-US-00014 Initiation: MeOTf 0.12 g (0.74 mmol; 1 eq) 1. Block: MeOx 2.23 g (26.2 mmol; 35 eq) 2. Block: cPrOx 1.64 g (13.1 mmol; 18 eq) 3. Block: MeOx 2.25 g (26.4 mmol; 36 eq) Termination: Boc-Pip 0.42 g (2.25 mmol; 3 eq) K.sub.2CO.sub.3 0.10 g (0.75 mmol; 1 eq) Solvent PhCN 15 mL Yield 5.36 g (0.65 mmol; 88%) of a white powder M 8.2 kg/mol GPC (HFIP) M.sub.n = 3.3 kg/mol; Ð = 1.17 .sup.1H-NMR M.sub.n = 8.0 kg/mol (Me-MeOx.sub.34-b-cPrOx.sub.18-b-MeOx.sub.34- PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.80-3.18 (br, 351H, N—CH.sub.2CH.sub.2); 3.07-2.93 (m, 3H, N—CH.sub.3); 2.20-1.98 (m, 206H, CO—CH.sub.3); 2.0-1.73 (br, 35H, N—CO—CH—(CH).sub.2, H.sub.2O); 1.49-1.39 (s, 8H, —C—(CH.sub.3).sub.3); 1.02-0.70 (d, 73H, CO—CH—(CH.sub.2).sub.2) ppm.
Me-MeOx.sub.35-PrOzi.sub.20-PipBoc (Reference Polymer)

##STR00042##

[0255] Me-MeOx.sub.35-b-PrOzi.sub.20-PipBoc was synthesized according to GSP 1

TABLE-US-00015 Initiation: MeOTf 0.18 g (1.1 mmol; 1 eq) 1. Block: MeOx 3.14 g (36.9 mmol; 35 eq) 2. Block: PrOzi 2.90 g (22.8 mmol; 20 eq) Termination: Boc-Pip 0.70 g (3.74 mmol; 3 eq) Solvent PhCN 12 mL Yield 4.91 g (0.86 mmol; 78%) of a white powder M 5.7 kg/mol GPC (HFIP) M.sub.n = 3.9 kg/mol; Ð = 1.12 .sup.1H-NMR M.sub.n = 6.3 kg/mol (Me-MeOx.sub.37-b-PrOzi.sub.23-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.72-3.38 (br, 150H, N—CH.sub.2CH.sub.2); 3.38-3.10 (br, 89H, N—CH.sub.2—CH.sub.2—CH.sub.2—); 3.08-2.93 (m, 3H, N—CH.sub.3); 2.33-2.18 (br, 45H, CO—CH.sub.2—CH.sub.2—CH.sub.3); 2.19-1.99 (m, 112H, CO—CH.sub.3); 1.94-1.54 (br, 114H, N—CH.sub.2—CH.sub.2—CH.sub.2—, CO—CH.sub.2—CH.sub.2—CH.sub.3); 1.51-1.43 (s, 11H, —C—(CH.sub.3).sub.3); 1.05-0.82 (m, 68H, CO—CH.sub.2—CH.sub.2—CH.sub.3) ppm.
Me-PrOzi.sub.20-MeOx.sub.35-PipBoc (Reference Polymer)

##STR00043##

[0256] Me-PrOzi.sub.20-b-MeOx.sub.35-PipBoc was synthesized according to GSP 1

TABLE-US-00016 Initiation: MeOTf 0.28 g (1.7 mmol; 1 eq) 1. Block: PrOzi 4.4 g (34.9 mmol; 20 eq) 2. Block: MeOx 5.08 g (61.2 mmol; 35 eq) Termination: Boc-Pip 0.96 g (5.10 mmol; 3 eq) Solvent PhCN 21 mL Yield 8.01 g (1.40 mmol; 82%) of a white powder M 5.7 kg/mol GPC (HFIP) M.sub.n = 3.7 kg/mol; Ð = 1.14 .sup.1H-NMR M.sub.n = 5.7 kg/mol (Me-PrOzi.sub.20-MeOx.sub.35-PipBoc) (CDCl.sub.3, 300.12 MHz; 298K): δ = 3.81-3.37 (br, 143H, N—CH.sub.2CH.sub.2); 3.37-3.11 (br, 84H, N—CH.sub.2—CH.sub.2—CH.sub.2—); 3.03-2.88 (m, 3H, N—CH.sub.3); 2.34-2.19 (br, 41H, CO—CH.sub.2—CH.sub.2—CH.sub.3); 2.19-1.99 (m, 106H, CO—CH.sub.3); 1.96-1.54 (br, 90H, N—CH.sub.2—CH.sub.2—CH.sub.2—, CO—CH.sub.2—CH.sub.2—CH.sub.3); 1.51-1.40 (s, 10H, —C—(CH.sub.3).sub.3); 1.04-0.84 (m, 61H, CO—CH.sub.2—CH.sub.2—CH.sub.3) ppm.

Tests

Nuclear Magnetic Resonance Spectroscopy (NMR)

[0257] NMR spectra were recorded on a Fourier 300 (′H; 300.12 MHz), Bruker Biospin (Rheinstetten, Germany) at 298 K. The spectra were calibrated to the signals of residual protonated solvent signals (CDCl.sub.3: 7.26 ppm; or to the internal standard sodium 3-(trimethylsilyl)tetradeuteriopropionat (TMSP) (0.00 ppm). Multiplicities of signals are depicted as follows: s, singlet; d, doublet; t, triplet; q, quartet; quin, quintet; dt; doublet of triplets; m, multiplet; b, broad.

Gel Permeation Chromatography (GPC)

[0258] Gel permeation chromatography (GPC) was performed on a Polymer Standard Service (PSS, Mainz, Germany) system (pump mod. 1260 infinity, RI-detector mod. 1260 infinity, precolumn GRAM 10 μM (50×8 mm), 30 Å PSS GRAM 10 μM (300×8 mm) and 1000 Å PSS GRAM 10 μM (300×8 mm)), with DMF (containing 1 g/L (11.5 mM) LiBr) or HFIP (containing 3 g/L potassium trifluoroacetate (KTFA)) as eluent and calibrated against PEG standards. Columns were kept at 40° C. and the flow rate was set to 1 mL/min (DMF) or 0.7 mL/min (HFIP). Prior to each measurement, samples were filtered through 0.2 μm teflon filter (Rotilabo, Karlsruhe).

Drug Solubilization

[0259] Polymer micelles loaded with the model drug curcumin (CUR) were prepared using the thin film method (R. Luxenhofer, A. Schulz, C. Rogues, S. Li, T. K. Bronich, E. V. Batrakova, R. Jordan, A. V. Kabanov, Biomaterials 2010, 31, 4972-4979). Ethanolic polymer (20 g/L for 10 g/L final polymer concentration; 50 g/L for 50 g/L final polymer concentration), paclitaxel (20 g/L) and curcumin (5.0 g/L) stock solutions or methanolic atorvastatin stock solutions (20 g/L) were mixed in desired ratio. After complete removal of the solvent at 50°-60° C., the films were dried in vacuo 0.2 mbar) for at least 3 hours (final polymer concentration: 10 g/L) or overnight (final polymer concentration: 50 g/L). Subsequently, preheated (37° C.) H.sub.2O (Millipore) or PBS was added to obtain final polymer and drug concentrations as tested. Complete solubilization was facilitated by shaking the solutions at 1250 rpm at 55° C. for 10 min-15 min (10 g/L polymer concentration) or at least 25 min (50 g/L polymer concentration) with a Thermomixer comfort, Eppendorf AG (Hamburg, Germany). Non-solubilized drug (if any) was removed by centrifugation for 5 min at 10.000 rpm (5.000 g) with a 3-Speed micro centrifuge, neoLab (Heidelberg, Germany). Solubilization experiments were performed with 3 samples and results are presented as means±standard deviation (SD).

[0260] Curcumin quantification was performed by UV-Vis absorption on a BioTek Eon Microplate Spectrophotometer, Thermo Fisher Scientific (MA, USA) using a calibration curve obtained with known amounts of CUR. Samples were prepared in Rotilabo F-Type 96 well plates, Carl Roth GmbH & Co. KG (Karlsruhe, Germany) with a constant volume of 100 μL. Spectra were recorded from 260-600 nm at a constant reading speed of 1 nm at 298 K. Curcumin absorption was detected at 428 nm. Prior to UV-Vis absorption measurements, the aqueous formulations got diluted with ethanol to give a final absorbance between 0.3 and 2.5 (diluted at least 1:20). The following equations were used to calculate loading capacity (LC) and loading efficiency (LE):

[00001]$\mathrm{LC}=\frac{m_{\mathrm{drug}}}{m_{\mathrm{drug}}+m_{\mathrm{excipient}}}.Math.100.Math.\%$$\mathrm{LE}=\frac{m_{\mathrm{drug}}}{m_{\mathrm{drug},\mathrm{added}}}.Math.100.Math.\%$

where m.sub.drug and m.sub.excipient are the weight amounts of the solubilized drug and polymer excipient in solution and m.sub.drug,added is the weight amount of the drug initially added to the dispersion. No loss of polymer during micelles preparation was assumed.

[0261] HPLC analysis was carried out on a LC-20A Prominence HPLC, Shimadzu (Duisburg, Germany) equipped with a system controller CBM-20A, a solvent delivery unit LC-20 AT (double plunger), an on-line degassing unit DGU-20A, an auto-sampler SIL-20AC, a photo-diode array detector SPD-M20A, a column oven CTO-20AC, and a refractive index detector RID-20A. As stationary phase, a ZORBAX Eclipse Plus, Agilent (Santa Clara, Calif., USA) C18 column (4.6×100 mm; 3.5 μm 50 mm×4 mm) was used.

[0262] Quantification of curcumin (CUR), demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), paclitaxel (PTX) and atorvastatin (Ator) was performed with a stepwise gradient. Within the first 10 min, the ratio of H.sub.2O/ACN was decreased from 60/40 (v/v) to 40/60 (v/v). Solvent ratio was kept constant for 5 min, prior to re-increase it to initial ratio of 60/40 (v/v) within 0.5 min. This ratio was kept for 5 min. Flow rate was 1 mL/min at 40° C. Detection was performed at 220 nm (PTX and Ator) and 425 nm (CUR, DMC, BDMC). Retention times R.sub.t were 9.6 min (PTX), 11.0 min (Ator), 8.1 min (CUR), 7.3 min (DMC) and 6.5 min (BDMC). Prior to each measurement, samples were centrifuged (10.000 rpm; 5000 g) with a Speed-micro centrifuge, neoLab (Heidelberg, Germany) and filtered through 0.4 μM filter (Rotilabo, Karlsruhe, Germany). Paclitaxel and Atorvastatin quantification was performed using a calibration curve obtained with known amounts of PTX and Ator, respectively. The results are shown in the tables below and in the annexed figures.

[0263] As shown in FIGS. 1 and 2, the reference polymer Prop-MeOx.sub.35-b-BuOx.sub.20-b-MeOx.sub.35-Pip exhibited loading capacities LCs up to 24.4±1.1 wt % (10 g/L polymer, FIG. 1) and 21.6±0.7 wt % (50 g/L polymer, FIG. 2) with corresponding amounts of solubilized CUR of 3.2±0.2 g/L and 13.7±0.5 g/L respectively. However, the polymers in accordance with the present invention, Prop-MeOx.sub.35-b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc and Prop-MeOx.sub.35-b-PrOzi.sub.20-b-MeOx.sub.35-PipBoc, exhibited outstanding high drug loadings of 37.4±0.5 g/L (with 50 g/L Prop-MeOx.sub.35-b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc, FIG. 2) and 54.5±0.2 g/L (with 50 g/L Prop-MeOx.sub.35-b-PrOzi.sub.20-b-MeOx.sub.35-PipBoc, FIG. 2).

[0264] The drug loading of Prop-MeOx.sub.35-b-BuOx.sub.20-b-MeOx.sub.35-Pip increased with increasing CUR feed. However, at CUR concentrations ≥5 g/L (10 g/L P2) and ≥30 g/L (50 g/L P2), respectively, the formulations collapsed and the amount of solubilized CUR dramatically decreased to almost 0 g/L. Prop-MeOx.sub.35-b-PrOzi.sub.20-b-MeOx.sub.35-PipBoc and Prop-MeOx.sub.35-b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc did not display this effect. As Prop-MeOx.sub.35-b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc reached its maximum CUR content (9.4 g/L CUR with 10 g/L polymer; 37.4 g/L CUR with 50 g/L polymer), additional CUR feed only marginally affected drug loadings, with more and more curcumin starting to precipitate.

TABLE-US-00017 TABLE 1 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by the reference polymer Prop-MeOx.sub.35-b-BuOx.sub.20-b-MeOx.sub.35-Pip. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 0.5 0.46 ± 0.01 92.1 ± 2.1  4.4 ± 0.1 1.0 0.88 ± 0.00 87.8 ± 0.5  8.1 ± 0.0 2.5 2.12 ± 0.10 84.7 ± 3.9  17.5 ± 0.7  3.5 3.23 ± 0.18 92.4 ± 5.4  24.4 ± 1.1  5.0 0.10 ± 0.00 2.0 ± 0.0 1.0 ± 0.0 7.5 0.10 ± 0.02 1.0 ± 0.3 0.7 ± 0.2

TABLE-US-00018 TABLE 2 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by Prop-MeOx.sub.35- b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 0.5 0.45 ± 0.02 89.4 ± 4.0  4.3 ± 0.2 1.0 0.89 ± 0.07 88.6 ± 7.4  8.1 ± 0.6 2.5 2.22 ± 0.14 88.8 ± 5.7  18.2 ± 1.0  3.5 2.73 ± 0.31 77.9 ± 8.82 21.4 ± 1.9  5.0 3.88 ± 0.54 77.6 ± 10.9 27.9 ± 2.8  7.5 5.52 ± 0.32 73.6 ± 4.3  35.5 ± 1.3 9.0 8.47 ± 0.07 94.2 ± 0.8  45.9 ± 0.2 10.5 9.42 ± 0.61 89.7 ± 5.8  48.5 ± 1.7 13 9.43 ± 0.38 72.5 ± 2.9  48.5 ± 1.0

TABLE-US-00019 TABLE 3 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by Prop-MeOx.sub.35-b- PrOzi.sub.20-b-MeOx.sub.35-PipBoc. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 0.5 0.38 ± 0.01 76.2 ± 1.7 3.7 ± 0.1 1.0 0.80 ± 0.03 80.4 ± 3.3 7.4 ± 0.3 2.5 2.28 ± 0.05 91.2 ± 2.0 18.6 ± 0.3  3.5 3.12 ± 0.15 89.2 ± 4.2 23.8 ± 0.8  5.0 4.45 ± 0.09 89.0 ± 1.8 30.8 ± 0.4  7.5 6.76 ± 0.05 90.1 ± 0.6 40.3 ± 0.2  9.0 8.52 ± 0.14 94.6 ± 1.5 46.0 ± 0.4 10.5 10.00 ± 0.18  95.2 ± 1.7 50.0 ± 0.4 13 11.91 ± 0.59  91.6 ± 4.5 54.3 ± 1.3

TABLE-US-00020 TABLE 4 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by the reference polymer Prop-MeOx.sub.35-b-BuOx.sub.20-b-MeOx.sub.35-Pip. Polymer concentration = 50 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 5 4.76 ± 0.20 93.1 ± 3.3  8.5 ± 0.3 10 8.67 ± 0.49 86.7 ± 4.9  14.8 ± 0.7  15 13.74 ± 0.53  91.6 ± 3.6  21.6 ± 0.7  20 8.45 ± 0.46 42.2 ± 2.3  14.5 ± 0.7  30 0.08 ± 0.07 0.3 ± 0.2 0.2 ± 0.2

TABLE-US-00021 TABLE 5 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by Prop-MeOx.sub.35-b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc. Polymer concentration = 50 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 5 4.76 ± 0.20 95.3 ± 3.9 8.7 ± 0.3 10 9.00 ± 0.57 90.0 ± 5.7 15.2 ± 0.8  15 13.62 ± 0.41  90.8 ± 2.7 21.4 ± 0.5  20 16.06 ± 0.94  80.3 ± 4.7 24.3 ± 1.1  30 28.08 ± 0.32  93.6 ± 1.1 36.0 ± 0.3  40 39.74 ± 0.72  93.6 ± 1.3 42.8 ± 0.3  60 39.62 ± 0.62  79.2 ± 1.5 41.9 ± 0.3 

TABLE-US-00022 TABLE 6 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by Prop-MeOx.sub.35-b-PrOzi.sub.20-b-MeOx.sub.35-PipBoc. Polymer concentration = 50 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 5 3.91 ± 0.17 78.2 ± 3.1 7.2 ± 0.3 10 8.79 ± 0.28 87.9 ± 2.6 14.9 ± 0.4  15 12.37 ± 0.12  82.5 ± 0.8 19.8 ± 0.1  20 16.12 ± 0.70  80.6 ± 3.3 24.4 ± 0.8  30 29.95 ± 0.61  99.8 ± 2.0 37.5 ± 0.5  40 39.74 ± 0.72  99.4 ± 1.8 44.3 ± 0.4  60 54.53 ± 0.15  90.9 ± 0.3 52.2 ± 0.1 

TABLE-US-00023 TABLE 7 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by the reference polymer Me-MeOx.sub.35-NonOx.sub.12-MeOx.sub.35-PipBoc. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 2 0.04 ± 0.00 2.2 ± 0.1 0.4 ± 0.0 4 0.45 ± 0.17 11.4 ± 4.2  4.3 ± 1.6 6 1.43 ± 0.13 23.8 ± 2.2  12.5 ± 1.3  8 3.21 ± 2.46 40.1 ± 30.7 24.3 ± 19.7 10 1.49 ± 0.68 14.9 ± 6.8  13.0 ± 6.4 

TABLE-US-00024 TABLE 8 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by Me-MeOx.sub.35-NonOzi.sub.11-MeOx.sub.35-PipBoc. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 2 1.97 ± 0.12 98.3 ± 5.8  16.4 ± 1.1  4 3.89 ± 0.30 97.3 ± 7.4  28.0 ± 2.9  6 4.46 ± 0.28 74.3 ± 4.6  30.8 ± 2.7  8 5.24 ± 2.75 65.5 ± 34.4 34.4 ± 21.6 10 7.90 ± 0.24 79.0 ± 2.4  44.1 ± 2.4  12 5.30 ± 3.61 44.2 ± 30.1 34.7 ± 26.5 14 1.68 ± 0.29 12.0 ± 2.0  14.4 ± 2.8 

TABLE-US-00025 TABLE 9 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by the reference polymer Me-MeOx.sub.36-EtHepOx.sub.13-MeOx.sub.36-PipBoc. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 2 0.00 ± 0.00  0.2 ± −0.1  0.0 ± 0.0 4 1.88 ± 0.14 47.1 ± 3.5  15.9 ± 1.4 6 2.79 ± 1.08 46.6 ± 17.9 21.8 ± 9.7 8 2.39 ± 0.45 29.8 ± 5.7  19.3 ± 4.3 10  3.33 ± 0.30 33.3 ± 3.0  25.0 ± 2.9

TABLE-US-00026 TABLE 10 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by Me-MeOx.sub.36-EtHepOzi.sub.11-MeOx.sub.36-PipBoc. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 2 2.15 ± 0.12 107.6 ± 6.1  17.7 ± 1.2 4 3.06 ± 0.21 76.5 ± 5.2 23.4 ± 2.0 6 3.81 ± 0.40 63.4 ± 6.7 27.6 ± 3.9 8 5.74 ± 0.44 71.8 ± 5.5 36.5 ± 4.2 10  4.39 ± 1.80  43.9 ± 18.0  30.5 ± 15.3

TABLE-US-00027 TABLE 11 Solubilized aqueous atorvastatin (Ator) concentrations, loading efficiencies LE and loading capacities LC in dependence of the atorvastatin feed by the reference polymer Prop-MeOx.sub.35-b-BuOx.sub.20-b- MeOx.sub.35-Pip. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). atorvastatin atorvastatin feed solublized LE LC [g/L] [g/L] [%] [%] 5 2.21 ± 1.13 44.2 ± 22.6 18.1 ± 10.1 8 2.65 ± 0.81 33.1 ± 10.1 20.9 ± 7.5 

TABLE-US-00028 TABLE 12 Solubilized aqueous atorvastatin (Ator) concentrations, loading efficiencies LE and loading capacities LC in dependence of the atorvastatin feed by Prop-MeOx.sub.35-b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). atorvastatin atorvastatin feed solublized LE LC [g/L] [g/L] [%] [%] 5 3.92 ± 0.45 78.4 ± 8.9 28.2 ± 4.3 8 5.84 ± 0.79 73.0 ± 9.9 36.9 ± 7.3

TABLE-US-00029 TABLE 13 Achieved co-formulated aqueous curcumin (CUR) and paclitaxel (PTX) concentrations, loading efficiencies LE and loading capacities LC in dependence of the drug feed concentrations. Polymer concentration Me-MeOx.sub.35-PrOzi.sub.20-MeOx.sub.35-PipBoc = 10 g/L. Data isgiven as means ± SD (n = 3). drug solubilized loading loading feed drug efficiency capacity drug [g/L] [g/L] [%] [%] Curcumin 2 2.20 ± 0.16 110.1 ± 8.2 18.0 ± 1.6 Paclitaxel 2 1.68 ± 0.03  84.0 ± 0.0 14.4 ± 0.3 CUR & PTX 4  3.88 97.0 28.0 Curcumin 4 4.24 ± 0.24 106.0 ± 6.0 29.8 ± 2.3 Paclitaxel 4 3.28 ± 0.04  82.0 ± 0.0 24.7 ± 0.4 CUR & PTX 8  7.52 94.0 42.9 Curcumin 6 5.07 ± 0.31  84.6 ± 5.2 33.7 ± 3.0 Paclitaxel 6 4.75 ± 0.00  79.1 ± 0.0 32.2 ± 0.3 CUR & PTX 12  9.82 81.8 49.5 Curcumin 8 7.68 ± 0.84  96.0 ± 10.6 43.4 ± 7.8 Paclitaxel 8 6.05 ± 0.10  75.7 ± 0.0 37.7 ± 1.0 CUR & PTX 16 13.73 85.8 57.9 Curcumin 10 7.12 ± 0.71 71.24 ± 7.1 41.6 ± 6.6 Paclitaxel 10 7.04 ± 0.37  70.4 ± 0.0 41.3 ± 3.5 CUR & PTX 20 14.16 70.8 58.6

TABLE-US-00030 TABLE 14 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by the polymer Me-MeOx.sub.35-b-cPrOx.sub.18-b-MeOx.sub.35-PipBoc (reference polymer). Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 2 1.04 ± 0.04 52.1 ± 1.9  9.4 ± 0.4 4 0.08 ± 0.06 2.0 ± 1.5 0.8 ± 0.6 6 0.55 ± 0.03 9.1 ± 0.5 5.2 ± 0.3 8 0.18 ± 0.02 2.3 ± 0.2 1.8 ± 0.2 10  0.05 ± 0.01 0.5 ± 0.1 0.5 ± 0.1 12  0.01 ± 0.00 0.1 ± 0.0 0.1 ± 0.0

TABLE-US-00031 TABLE 15 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by the polymer Me-MeOx.sub.36-b-cPrOzi.sub.18-b-MeOx.sub.36-PipBoc. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 2 1.96 ± 0.04 97.9 ± 2.1 16.4 ± 0.4 4 3.65 ± 0.07 91.3 ± 1.7 26.7 ± 0.7 6 5.22 ± 0.21 86.9 ± 3.4 34.3 ± 2.0 8 7.14 ± 0.16 89.2 ± 2.0 41.7 ± 1.6 10 8.00 ± 0.05 80.0 ± 0.5 44.4 ± 0.5 12 11.60 ± 0.26  96.7 ± 2.1 53.7 ± 2.5

TABLE-US-00032 TABLE 16 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by the polymer Me-MeOx.sub.35-b-iPrOx.sub.20-b-MeOx.sub.35-PipBoc (reference polymer). Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 2 1.59 ± 0.09 79.7 ± 4.7 13.7 ± 0.9  4 1.50 ± 0.04 37.4 ± 1.0 13.0 ± 0.4  6 0.81 ± 0.09 13.4 ± 1.6 7.5 ± 0.9 8 0.73 ± 0.02  9.1 ± 0.2 6.8 ± 0.2 10 0.49 ± 0.01  4.9 ± 0.1 4.6 ± 0.1 12 0.66 ± 0.12  5.5 ± 1.0 6.2 ± 1.1

TABLE-US-00033 TABLE 17 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by the polymer Me-MeOx.sub.35-b-iPrOzi.sub.20-b-MeOx.sub.35-PipBoc. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 2 1.80 ± 0.06 89.9 ± 3.1 15.2 ± 0.6 4 3.49 ± 0.04 87.3 ± 1.1 25.9 ± 0.4 6 5.25 ± 0.20 87.5 ± 3.4 34.4 ± 2.0 8 6.70 ± 0.17 83.7 ± 2.1 40.1 ± 1.7 10 8.80 ± 0.78 88.0 ± 7.8 46.8 ± 7.3 12 6.84 ± 1.02 57.0 ± 8.5 40.6 ± 9.3

TABLE-US-00034 TABLE 18 Solubilized aqueous paclitaxel (PTX) concentrations, loading efficiencies LE and loading capacities LC in dependence of the Paclitaxel feed by the polymer Me-MeOx.sub.35-b-cPrOx.sub.18-b-MeOx.sub.35-PipBoc (reference polymer). Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). paclitaxel solubilized feed paclitaxel LE LC [g/L] [g/L] [%] [%] 2 0.05 ± 0.00 2.6 ± 0.1 0.5 ± 0.0 4 0.09 ± 0.02 2.3 ± 0.5 0.9 ± 0.2 6 0.10 ± 0.02 1.7 ± 0.3 1.0 ± 0.2 8 0.06 ± 0.01 0.7 ± 0.1 0.6 ± 0.1 10 0.07 ± 0.04 0.7 ± 0.4 0.7 ± 0.4 12 0.05 ± 0.00 0.4 ± 0.0 0.5 ± 0.0

TABLE-US-00035 TABLE 19 Solubilized aqueous paclitaxel (PTX) concentrations, loading efficiencies LE and loading capacities LC in dependence of the paclitaxel feed by the polymer Me-MeOx.sub.36-b-cPrOzi.sub.18-b-MeOx.sub.36-PipBoc. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). paclitaxel solubilized feed paclitaxel LE LC [g/L] [g/L] [%] [%] 2 1.83 ± 0.07 91.3 ± 3.3 15.4 ± 0.7 4 2.99 ± 0.07 74.8 ± 1.7 23.0 ± 0.7 6 1.95 ± 0.19 32.5 ± 3.2 16.3 ± 1.9 8 0.58 ± 0.11  7.2 ± 1.4  5.5 ± 1.1 10 0.57 ± 0.33  5.7 ± 3.3  5.4 ± 3.2 12 0.55 ± 0.19  4.6 ± 1.6  5.2 ± 1.9

TABLE-US-00036 TABLE 20 Solubilized aqueous paclitaxel (PTX) concentrations, loading efficiencies LE and loading capacities LC in dependence of the paclitaxel feed by the polymer Me-MeOx.sub.35-b-iPrOx.sub.20-b-MeOx.sub.35-PipBoc (reference polymer). Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). paclitaxel solubilized feed paclitaxel LE LC [g/L] [g/L] [%] [%] 2 1.02 ± 0.09 50.9 ± 4.5  9.2 ± 0.9 4 0.47 ± 0.10 11.7 ± 2.6  4.5 ± 1.0 6 0.13 ± 0.06 2.2 ± 1.0 1.3 ± 0.6 8 0.10 ± 0.02 1.2 ± 0.3 0.9 ± 0.2 10 0.09 ± 0.04 0.9 ± 0.4 0.9 ± 0.4 12 0.08 ± 0.04 0.6 ± 0.3 0.8 ± 0.4

TABLE-US-00037 TABLE 21 Solubilized aqueous paclitaxel (PTX) concentrations, loading efficiencies LE and loading capacities LC in dependence of the paclitaxel feed by the polymer Me-MeOx.sub.35-b-iPrOzi.sub.20-b-MeOx.sub.35-PipBoc. Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). paclitaxel solubilized feed paclitaxel LE LC [g/L] [g/L] [%] [%] 2 1.60 ± 0.07 80.0 ± 3.5  13.8 ± 0.7   4 1.73 ± 0.21 43.2 ± 5.2  14.7 ± 2.1  6 0.55 ± 0.16 9.1 ± 2.7 5.2 ± 1.6 8 0.29 ± 0.26 3.7 ± 3.2 2.9 ± 2.5 10 0.06 ± 0.01 0.6 ± 0.1 0.6 ± 0.1 12 0.09 ± 0.03 0.8 ± 0.2 0.9 ± 0.3

TABLE-US-00038 TABLE 22 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by the polymer Me-MeOx.sub.35-b-cPrOzi.sub.18-PipBoc (reference polymer). Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 2 1.85 ± 0.03 92.4 ± 1.7  15.6 ± 0.3  4 3.56 ± 0.17 88.9 ± 4.2  26.2 ± 1.7  6 0.11 ± 0.04 1.9 ± 0.6 1.1 ± 0.4 8 0.03 ± 0.00 0.4 ± 0.0 0.3 ± 0.0 10 0.03 ± 0.01 0.3 ± 0.1 0.3 ± 0.1 12 0.04 ± 0.01 0.3 ± 0.1 0.4 ± 0.1

TABLE-US-00039 TABLE 23 Solubilized aqueous curcumin (CUR) concentrations, loading efficiencies LE and loading capacities LC in dependence of the curcumin feed by the polymer Me-PrOzi.sub.18-b-MeOx.sub.35-PipBoc (reference polymer). Polymer concentration = 10 g/L. Data is given as means ± SD (n = 3). curcumin solubilized feed curcumin LE LC [g/L] [g/L] [%] [%] 2 1.84 ± 0.13 91.8 ± 6.6  15.5 ± 1.3  4 3.40 ± 0.04 84.9 ± 1.1  25.4 ± 0.4  6 0.49 ± 0.15 8.2 ± 2.5 4.7 ± 1.4 8 0.06 ± 0.01 0.8 ± 0.1 0.6 ± 0.1 10 0.05 ± 0.01 0.5 ± 0.1 0.5 ± 0.1 12 0.03 ± 0.01 0.3 ± 0.1 0.3 ± 0.1

DISCUSSION OF FIGURES

[0265] FIG. 1 shows solubilized aqueous curcumin (CUR) concentrations (bars, left axis) and the corresponding loading capacities (lines, right axis) in dependence of the CUR feed by Prop-MeOx.sub.35-b-BuOx.sub.20-b-MeOx.sub.35-Pip (reference polymer, empty bars, dashed line), Prop-MeOx.sub.35-b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc (striped bars, dotted line) and Prop-MeOx.sub.35-b-PrOzi.sub.20-b-MeOx.sub.35-PipBoc (black bars, solid line). Polymer concentration=10 g/L. Data is given as means±SD (n=3).

[0266] FIG. 2 shows solubilized aqueous curcumin (CUR) concentrations (bars, left axis) and the corresponding loading capacities (lines, right axis) in dependence of the CUR feed by Prop-MeOx.sub.35-b-BuOx.sub.20-b-MeOx.sub.35-Pip (reference polymer, empty bars, dashed line), Prop-MeOx.sub.35-b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc (striped bars, dotted line) and Prop-MeOx.sub.35-b-PrOzi.sub.20-b-MeOx.sub.35-PipBoc (black bars, solid line). Polymer concentration=50 g/L. Data is given as means±SD (n=3).

[0267] FIG. 3 shows solubilized aqueous curcumin (CUR) concentrations (bars, left axis) and the corresponding loading capacities (lines, right axis) in dependence of the CUR feed by Me-MeOx.sub.35-NonOx.sub.12-MeOx.sub.35-PipBoc (empty bars, dashed line), Me-MeOx.sub.35-NonOzi.sub.12-MeOx.sub.35PipBoc (black bars, solid line). Polymer concentration=10 g/L. Data is given as means±SD (n=3).

[0268] FIG. 4 shows solubilized aqueous curcumin (CUR) concentrations (bars, left axis) and the corresponding loading capacities (lines, right axis) in dependence of the CUR feed by Me-MeOx.sub.35-EtHepOx.sub.12-MeOx.sub.35-PipBoc (empty bars, dashed line), Me-MeOx.sub.35-EtHepOzi.sub.12-MeOx.sub.35PipBoc (black bars, solid line). Polymer concentration=10 g/L. Data is given as means±SD (n=3).

[0269] FIG. 5 shows solubilized aqueous atorvastatin (Ator) concentrations (bars, left axis) and the corresponding loading capacities (lines, right axis) in dependence of the atorvastatin feed by Prop-MeOx.sub.35-b-BuOx.sub.20-b-MeOx.sub.35-Pip (reference polymer, empty bars, dashed line) and Prop-MeOx.sub.35-b-BuOzi.sub.20-b-MeOx.sub.35-PipBoc (striped bars, dotted line) Polymer concentration=50 g/L. Data is given as means±SD (n=3).

[0270] FIG. 6 shows solubilized aqueous curcumin (CUR) concentrations in dependence of the CUR feed by Me-MeOx.sub.35-b-iPrOx.sub.20-b-MeOx.sub.35-PipBoc Polymer (reference polymer) concentration=10 g/L. Data is given as means±SD (n=3).

[0271] FIG. 7 shows solubilized aqueous curcumin (CUR) concentrations in dependence of the CUR feed by Me-MeOx.sub.35-b-iPrOzi.sub.20-b-MeOx.sub.35-PipBoc Polymer concentration=10 g/L. Data is given as means±SD (n=3).

[0272] FIG. 8 shows solubilized aqueous curcumin (CUR) concentrations in dependence of the CUR feed by Me-MeOx.sub.35-b-cPrOx.sub.18-b-MeOx.sub.35-PipBoc Polymer (reference polymer) concentration=10 g/L. Data is given as means±SD (n=3).

[0273] FIG. 9 shows solubilized aqueous curcumin (CUR) concentrations in dependence of the CUR feed by Me-MeOx.sub.36-b-cPrOzi.sub.10-b-MeOx.sub.36-PipBoc Polymer concentration=10 g/L. Data is given as means±SD (n=3).

[0274] FIG. 10 shows solubilized aqueous paclitaxel (PTX) concentrations in dependence of the PTX feed by Me-MeOx.sub.35-b-iPrOx.sub.20-b-MeOx.sub.35-PipBoc Polymer (reference polymer) concentration=10 g/L. Data is given as means±SD (n=3).

[0275] FIG. 11 shows solubilized aqueous paclitaxel (PTX) concentrations in dependence of the PTX feed by Me-MeOx.sub.35-b-iPrOzi.sub.20-b-MeOx.sub.35-PipBoc Polymer concentration=10 g/L. Data is given as means±SD (n=3).

[0276] FIG. 12 shows solubilized aqueous paclitaxel (PTX) concentrations in dependence of the PTX feed by Me-MeOx.sub.35-b-cPrOx.sub.10-b-MeOx.sub.35-PipBoc Polymer (reference polymer) concentration=10 g/L. Data is given as means±SD (n=3).

[0277] FIG. 13 shows solubilized aqueous paclitaxel (PTX) concentrations in dependence of the PTX feed by Me-MeOx.sub.36-b-cPrOzi.sub.10-b-MeOx.sub.36-PipBoc Polymer concentration=10 g/L. Data is given as means±SD (n=3).

[0278] FIG. 14 shows solubilized aqueous curcumin (CUR) concentrations in dependence of the CUR feed by Me-MeOx.sub.35-b-PrOzi.sub.20-PipBoc (reference polymer). Polymer concentration=10 g/L. Data is given as means±SD (n=3).

[0279] FIG. 15 shows solubilized aqueous curcumin (CUR) concentrations in dependence of the CUR feed by Me-PrOzi.sub.20-b-MeOx.sub.35-PipBoc (reference polymer). Polymer concentration=10 g/L. Data is given as means±SD (n=3).