Table 1.
Colloid-Forming Drugs with pKa’s > 5 Show pH-Dependent Critical Aggregation Concentrations (CACs) between Physiological pH 7.4 and Endosomal pH 5.5a
| Drug name | Structure and protonation site | Critical aggregation concentration (μM) |
pKa of DH+ | ||
|---|---|---|---|---|---|
| pH 7.4 | pH 5.5 | ||||
| pH-responsive | Lapatinib |  |
1.2 ± 0.3 | 17 ± 3 | 7.2 |
| Clotrimazole |  |
24 ± 1 | ~100 | 6.62 | |
| Nilotinib |  |
4.4 ± 1.4 | 15 ± 5 | 6.3 | |
| Pazopanib |  |
20 ± 4 | ~100 | 5.07 | |
| Unresponsive | Sorafenib |  |
5.9 ± 0.5 | 2.4 ± 1.1 | 2.03 |
| Fulvestrant |  |
1.4 ± 0.4 | 1.6 ± 0.0 | −0.88 | |
a
CACs were measured in pH-adjusted phosphate buffered saline (PBS) by dynamic light scattering as described in the Supporting Information (n = 3, mean ± 95% CI) and pKa’s were obtained from DrugBank.ca.