Mirdametinib (PD0325901) Liposomes, Formulation U6-2

Figure 2. DLS analysis of Mirdametinib Liposomes, Formulation u6-1 (batch 26734). The average size and PDI of triplicate measurements are annotated on the representative snapshot from DLS data acquisition screen. The data are representative of a typical batch.

Figure 3. In vivo imaging of Mirdametinib liposomes labeled with fluorescent dyes. NSG mice with SKOV3 tumors received one i.v. injection of DiR or DiD labeled Mirdametinib liposomes (mouse on the left and in middle, respectively), or unlabeled (mouse on right). The top and bottom images are of the same mice, showing different IVIS filter sets for DiR or DiD, respectively. The images were acquired using default setting ~48 hr after injection of the liposomes. Accumulation of U6-1 in tumors by EPR effect can be seen by the representative images. The low intensity fluorescence in the DiR mouse corresponds to the liver. The exposure has been adjusted to show highest intensity signal in the tumor. In the raw images, all organs will emit fluorescence, but signal intensity is highest in the tumors. The PEGylation of U6-1 formulation aids in the EPR accumulation into tumor tissue by reducing RES uptake. Product SKU according to mouse: Left, DLL-0008-1C (DiR-labeled); Middle, DLL-0008-1B (DiD-labeled); Right, DLL-0008-1A (unlabeled). Other fluorescent-labeled versions (DiI, DiO) should be detectable provided appropriate filter sets are available. DiD appears similar to APC on flow cytometry and may be used to track cellular uptake (not shown). Other modifications to this formulation are available upon request.