Table 4. Results of USP rabbit pyrogen test on adjuvant loaded unmodified, phospholipid-PEG and Pluronic modified liposomes.
Formulation | Assay outcome NPa or Pb (Individual temperature change values for three rabbits) | Fold improvement over aqueous CRX-601c | |
---|---|---|---|
Dose of 250 ng/kg | Dose of 500 ng/kg | ||
CRX-601/Unmodified liposome | NP (0.0 °C, 0.0 °C, 0.0 °C) | NP (0.0 °C, 0.3 °C, 0.0 °C) | 500 |
| |||
Phospholipid-PEG modified liposomes | |||
| |||
CRX-601/5 mol% PE-PEG2K liposome | NP (0.0 °C, 0.1 °C, 0.0 °C) | NP (0.0 °C, 0.0 °C, 0.2 °C) | 500 |
CRX-601/25 mol% PE-PEG2K liposome | NP (0.1 °C, 0.0 °C, 0.0 °C) | NP (0.1 °C, 0.3 °C, 0.0 °C) | 500 |
CRX-601/5 mol% PE-PEG5K liposome | NP (0.3 °C, 0.2 °C, 0.0 °C) | NP (0.0 °C, 0.0 °C, 0.4 °C) | 500 |
CRX-601/25 mol% PE-PEG5K liposome | NP (0.3 °C, 0.0 °C, 0.3 °C) | NP (0.3 °C, 0.0 °C, 0.0 °C) | 500 |
| |||
Pluronic modified liposomes | |||
| |||
CRX-601 /15 mol% L64 liposomes | P (0.3 °C, 0.6 °C, 0.7 °C) | P (0.8 °C, 0.8 °C, 0.4 °C) | 125d |
CRX-601 /25 mol% L64 liposomes | P (0.9 °C, 0.5 °C, 0.9 °C) | P (0.5 °C, 0.6 °C, 0.9 °C) | 125d |
CRX-601/ 15 mol% F68 liposomes | NP (0.0 °C, 0.0 °C, 0.4 °C) | P (0.5 °C, 0.4 °C, 0.8 °C) | 250 |
CRX-601 /25 mol% F68 liposomes | NP (0.0 °C, 0.1 °C, 0.0 °C) | P (0.3 °C, 0.7 °C, 0.4 °C) | 250 |
CRX-601/15 mol% F127 liposome | NP (0.2 °C, 0.0 °C, 0.1 °C) | NP (0.0 °C, 0.3 °C, 0.0 °C) | 500 |
CRX-601/25 mol% F127 liposomes | NP (0.4 °C, 0.2 °C, 0.4 °C) | P (0.3 °C, 0.3 °C, 0.5 °C) | 250 |
NP: Non-pyrogenic response
P: Pyrogenic response. The test is considered NP if none of the rabbits shows an individual temperature rise of 0.5 °C or more above its respective control temperature at any point.
Maximum non-pyrogenic dose of aqueous CRX-601 is 1 ng/kg.
The formulations were non-pyrogenic at 125 ng/Kg (individual temperature changes not shown).