Table 1.
Physiochemical characterization of epothilone D pilot formulations with iron-hydroxamate or disulfide bond stabilization. Formulations were performed with each polymer listed as an entry number and characterized by drug weight loading, efficiency, particle size, and dialysis above and below the critical micelle concentration. Entry numbers 1 and 7 represent the leads selected for screening, and entry number 2 represents the scaled-up lead formulation.
| Entry number | Polymer core block | Polymer stabilizing block | Weight loading (% w/w) | Efficiency (%) | Average diameter (nm) | Dialysis > CMC (% remaining) | Dialysis < CMC (% remaining) |
|---|---|---|---|---|---|---|---|
| 1 | D-Phe15/ L-Tyr15/ D-Leu10 |
NHOH | 3.4 | 66 | 70 | 90 | 60 |
| 2 | D-Phe15/ L-Tyr15/ D-Leu10 |
NHOH | 4.4 | 91 | 75 | 94 | 68 |
| 3 | D-Phe15/ L-Tyr25 |
NHOH | 3.3 | 64 | 70 | 80 | 25 |
| 4 | D-Phe15/ L-Tyr20/ D-Leu5 |
NHOH | 3.0 | 58 | 91 | 91 | 28 |
| 5 | D-Phe15/ L-Tyr20/ D-Asp5 |
NHOH | 1.7 | 33 | 97 | 82 | 28 |
| 6 | D-Phe10/ L-Tyr20/ D-Asp10 |
NHOH | 0.9 | 17 | >200 | 55 | <10 |
| 7 | L-Tyr20/ D-Leu20 |
Cysteine | 3.7 | 72 | 68 | 94 | 38 |
| 8 | D-Phe15/ L-Tyr25 |
Cysteine | 2.9 | 56 | 86 | 87 | 11 |
| 9 | D-Phe15/ L-Asp25 |
Cysteine | 0.1 | <1 | 35 | ND | ND |
| 10 | L-Tyr20/ D-Asp20 |
Cysteine | 0.1 | <1 | >200 | 47 | <10 |
| 11 | D-Leu15/ L-Tyr20/ D-Asp20 |
Cysteine | 0.5 | 1 | >200 | ND | ND |